Alternative 3'UTR expression induced by T cell activation is regulated in a temporal and signal dependent manner.

The length of 3' untranslated regions (3'UTR) is highly regulated during many transitions in cell state, including T cell activation, through the process of alternative polyadenylation (APA). However, the regulatory mechanisms and functional consequences of APA remain largely unexplored. Here we present a detailed analysis of the temporal and condition-specific regulation of APA following activation of primary human CD4+ T cells. We find that global APA changes are regulated temporally and CD28 costimulatory signals enhance a subset of these changes. Most APA changes upon T cell activation involve 3'UTR shortening, although a set of genes enriched for function in the mTOR pathway exhibit 3'UTR lengthening. While upregulation of the core polyadenylation machinery likely induces 3'UTR shortening following prolonged T cell stimulation; a significant program of APA changes occur prior to cellular proliferation or upregulation of the APA machinery. Motif analysis suggests that at least a subset of these early changes in APA are driven by upregulation of RBM3, an RNA-binding protein which competes with the APA machinery for binding. Together this work expands our understanding of the impact and mechanisms of APA in response to T cell activation and suggests new mechanisms by which APA may be regulated.

A mitochondrial surveillance mechanism activated by SRSF2 mutations in hematologic malignancies.

Splicing factor mutations are common in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but how they alter cellular functions is unclear. We show that the pathogenic SRSF2P95H/+ mutation disrupts the splicing of mitochondrial mRNAs, impairs mitochondrial complex I function, and robustly increases mitophagy. We also identified a mitochondrial surveillance mechanism by which mitochondrial dysfunction modifies splicing of the mitophagy activator PINK1 to remove a poison intron, increasing the stability and abundance of PINK1 mRNA and protein. SRSF2P95H-induced mitochondrial dysfunction increased PINK1 expression through this mechanism, which is essential for survival of SRSF2P95H/+ cells. Inhibition of splicing with a glycogen synthase kinase 3 inhibitor promoted retention of the poison intron, impairing mitophagy and activating apoptosis in SRSF2P95H/+ cells. These data reveal a homeostatic mechanism for sensing mitochondrial stress through PINK1 splicing and identify increased mitophagy as a disease marker and a therapeutic vulnerability in SRSF2P95H mutant MDS and AML.

A mitochondrial surveillance mechanism activated by SRSF2 mutations in hematologic malignancies.

Splicing factor mutations are common in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but how they alter cellular functions is unclear. We show that the pathogenic SRSF2P95H/+ mutation disrupts the splicing of mitochondrial mRNAs, impairs mitochondrial complex I function, and robustly increases mitophagy. We also identified a mitochondrial surveillance mechanism by which mitochondrial dysfunction modifies splicing of the mitophagy activator PINK1 to remove a poison intron, increasing the stability and abundance of PINK1 mRNA and protein. SRSF2P95H-induced mitochondrial dysfunction increased PINK1 expression through this mechanism, which is essential for survival of SRSF2P95H/+ cells. Inhibition of splicing with a glycogen synthase kinase 3 inhibitor promoted retention of the poison intron, impairing mitophagy and activating apoptosis in SRSF2P95H/+ cells. These data reveal a homeostatic mechanism for sensing mitochondrial stress through PINK1 splicing and identify increased mitophagy as a disease marker and a therapeutic vulnerability in SRSF2P95H mutant MDS and AML.

Satisfaction with social connectedness is associated with depression and anxiety symptoms in neurodiverse first-semester college students.

LAY ABSTRACT: How satisfied people feel with their social connections and support is related to mental health outcomes for many different types of people. People may feel less socially connected at some times in their life-like when they start college. Feeling disconnected from others could lead to depression or anxiety. The transition to college may be especially difficult for autistic students as they are more likely to have difficulties adjusting socially. In our study, we asked 263 college students to answer questions about their emotions and social satisfaction twice per week during their first semester of college. We found that students who reported being less satisfied with their social connectedness (either at the beginning or throughout the semester) tended to express more symptoms of depression and anxiety. This relationship between social satisfaction and anxiety was even stronger for people who had a strong desire for social interaction (i.e. were more socially motivated). Students with more autistic traits tended to report more mood concerns, and they also reported being less satisfied with friendships at the beginning of the semester. This information may help to support ongoing efforts to better address mental health in autistic college students by encouraging efforts to improve social satisfaction.

Stigma and knowledge about autism in Brazil: A psychometric and intervention study.

LAY ABSTRACT: To promote the full inclusion of autistic people, we must change the knowledge and attitudes of non-autistic individuals. Unfortunately, access to autism information and support remains limited in Brazil, and stigma is also common. Brazilian researchers reached out to a researcher in the United States to co-develop Brazilian surveys to measure autism stigma and knowledge. Together, they made Brazilian versions of stigma and knowledge surveys which autistic people in the United States had helped make. They also adapted an online autism training used in other countries with help from three Brazilian autistic people and the mother of an autistic child. They used the new measures to see if the autism training improved autism stigma and knowledge among Brazilians. The surveys, called EARPA and ECAT in Brazil, were translated into Portuguese in a previous study. In the first study in this article, 532 Brazilians completed the stigma measure and 510 completed the knowledge measure. The researchers used exploratory graph analysis, which uses the connections between items in a survey to understand which items belong together. Seventy-nine Brazilians participated in the training. They were mostly white, female university students. The EGA showed that the stigma survey measured one big idea while the knowledge survey measured four ideas: diagnosis/cause; socio-communicative development; stimming and special interests; and autism in adulthood. Both scales are promising and may be helpful in future Brazilian and cross-cultural studies about autism. Participants reported more knowledge and less stigma after the autism training, which has been found in other countries too.

Time to level up: A systematic review of interventions aiming to reduce stigma toward autistic people.

LAY ABSTRACT: How non-autistic people think about autistic people impacts autistic people negatively. Many studies developed trainings to reduce autism stigma. The existing trainings vary a lot in terms of study design, content, and reported effectiveness. This means that a review studying how the studies have been conducted is needed. We also looked at the quality of these studies. We collected and studied 26 studies that tried to reduce stigma toward autistic people. The studies often targeted White K-12 students and college students. Most trainings were implemented once. Trainings frequently used video or computer. Especially, recent studies tended to use online platforms. The study quality was poor for most studies. Some studies made inaccurate claims about the intervention effectiveness. Studies did not sufficiently address study limitations. Future trainings should aim to figure out why and how interventions work. How intervention changes people's behavior and thoughts should be studied. Researchers should study whether the training can change the societal stigma. Also, researchers should use a better study design.

MAJIQlopedia: an encyclopedia of RNA splicing variations in human tissues and cancer.

Quantification of RNA splicing variations based on RNA-Sequencing can reveal tissue- and disease-specific splicing patterns. To study such splicing variations, we introduce MAJIQlopedia, an encyclopedia of splicing variations that encompasses 86 human tissues and 41 cancer datasets. MAJIQlopedia reports annotated and unannotated splicing events for a total of 486 175 alternative splice junctions in normal tissues and 338 317 alternative splice junctions in cancer. This database, available at https://majiq.biociphers.org/majiqlopedia/, includes a user-friendly interface that provides graphical representations of junction usage quantification for each junction across all tissue or cancer types. To demonstrate case usage of MAJIQlopedia, we review splicing variations in genes WT1, MAPT and BIN1, which all have known tissue or cancer-specific splicing variations. We also use MAJIQlopedia to highlight novel splicing variations in FDX1 and MEGF9 in normal tissues, and we uncover a novel exon inclusion event in RPS6KA6 that only occurs in two cancer types. Users can download the database, request the addition of data to the webtool, or install a MAJIQlopedia server to integrate proprietary data. MAJIQlopedia can serve as a reference database for researchers seeking to understand what splicing variations exist in genes of interest, and those looking to understand tissue- or cancer-specific splice isoform usage.

Repetitive Negative Thinking As a Transdiagnostic Prospective Predictor of Depression and Anxiety Symptoms in Neurodiverse First-Semester College Students.

Background: Improving the understanding and treatment of mental health concerns, including depression and anxiety, are significant priorities for autistic adults. While several theories have been proposed to explain the high prevalence of internalizing symptoms in autistic populations, little longitudinal research has been done to investigate potential causal mechanisms. Additional research is needed to explore how proposed contributors to depression from general population research predict and/or moderate the development of internalizing symptoms in autistic individuals. In this study, we investigated the relation of one established risk factor, repetitive negative thinking (RNT), to internalizing symptoms over the course of college students' first semester, additionally examining whether this association is moderated by a measure of autistic traits. Methods: Students were recruited from 4 northeastern U.S. universities: 144 participating students included 97 nonautistic students and 47 participants who either reported a formal autism diagnosis (n = 15) or endorsed a history of self and/or others thinking that they may be autistic (n = 32). Participants completed a baseline survey battery within their first 2 weeks of starting college, a brief biweekly survey throughout their first semester (up to 24 times across 12 weeks), and an endpoint packet. Results: Elevated trait-like RNT at baseline was prospectively associated with biweekly ratings of depression and anxiety symptoms across the semester. In addition, greater RNT was synchronously related to elevated sadness, anhedonia, and anxiety throughout the semester. Contrary to hypotheses, a shorter term predictive relationship between RNT at one timepoint and mood symptoms at the next was largely unsupported. While these patterns were observed across neurotypes, students with higher self-reported autistic traits were more likely to experience RNT, as well as depressive and anxiety symptoms. Conclusions: These preliminary findings highlight RNT as a specific mechanism that may be a useful prevention and/or intervention target toward reducing the elevated depression and anxiety rates in the autistic community.

Why was this study done?: Many autistic people have depression and anxiety. However, we know very little about why autistic people are more likely to have these mental health concerns than people who are not autistic. We also do not know what leads to these symptoms over time. One theory is that repetitive negative thinking (RNT; or thinking repeatedly about problems and worries) might cause depression and anxiety. Autistic people might do more RNT than nonautistic people. What was the purpose of this study?: In this study, we wanted to see how RNT might relate to depression and anxiety over the first semester of college. We looked at how this might be related to autistic traits. What did the researchers do?: The researchers gave surveys to 144 students about their experiences with depression, anxiety, and RNT. The participants answered these surveys at the beginning and end of their first semester at their university. They also completed a brief survey 24 times (twice per week for 12 weeks) during the semester. What were the results of the study?: We found that overall RNT levels at the beginning of the semester were related to sadness, anhedonia (lack of pleasure), and anxiety later. In-the-moment RNT reported on the twice-weekly survey was also related to sadness, anhedonia, and anxiety. However, RNT on biweekly surveys did not seem to predict mood symptoms a few days later. Students with higher levels of autistic traits tended to report more depression and anxiety, as well as more RNT. What do these findings add to what was already known?: This study helps us to understand that RNT might be related to depression and anxiety, regardless of whether or not someone is autistic. This might mean that reducing RNT could help prevent or treat depression and anxiety, especially in autistic adults. What are potential weaknesses in the study?: Our study had a low number of participants with formal autism diagnoses (15 people), so it might not represent the broader population of autistic adults with formal diagnoses as well as we would like. Nevertheless, we had a larger group with self-reported or suspected autism (32 people). How will these findings help autistic adults now or in the future?: These findings help us to better understand risk factors for depression and anxiety in autistic adults. Since RNT was related to depression and anxiety in the same way regardless of levels of autistic traits in our study, we hope that clinicians will feel more comfortable providing therapy to people with mood disorders, regardless of whether they are autistic and/or have high autistic traits. This could be a small step toward increasing equity and accessibility of mental health services for autistic adults.

Cryptic MHC-E epitope from influenza elicits a potent cytolytic T cell response.

The extent to which unconventional forms of antigen presentation drive T cell immunity is unknown. By convention, CD8 T cells recognize viral peptides, or epitopes, in association with classical major histocompatibility complex (MHC) class I, or MHC-Ia, but immune surveillance can, in some cases, be directed against peptides presented by nonclassical MHC-Ib, in particular the MHC-E proteins (Qa-1 in mice and HLA-E in humans); however, the overall importance of nonclassical responses in antiviral immunity remains unclear. Similarly uncertain is the importance of 'cryptic' viral epitopes, defined as those undetectable by conventional mapping techniques. Here we used an immunopeptidomic approach to search for unconventional epitopes that drive T cell responses in mice infected with influenza virus A/Puerto Rico/8/1934. We identified a nine amino acid epitope, termed M-SL9, that drives a co-immunodominant, cytolytic CD8 T cell response that is unconventional in two major ways: first, it is presented by Qa-1, and second, it has a cryptic origin, mapping to an unannotated alternative reading frame product of the influenza matrix gene segment. Presentation and immunogenicity of M-SL9 are dependent on the second AUG codon of the positive sense matrix RNA segment, suggesting translation initiation by leaky ribosomal scanning. During influenza virus A/Puerto Rico/8/1934 infection, M-SL9-specific T cells exhibit a low level of egress from the lungs and strong differentiation into tissue-resident memory cells. Importantly, we show that M-SL9/Qa-1-specific T cells can be strongly induced by messenger RNA vaccination and that they can mediate antigen-specific cytolysis in vivo. Our results demonstrate that noncanonical translation products can account for an important fraction of the T cell repertoire and add to a growing body of evidence that MHC-E-restricted T cells could have substantial therapeutic value.

Evaluation of an Autism Training in a Much-Needed Context: The Case of France.

Background: Autistic people in France have called for community education to reduce autism stigma. As such, training is needed to help university students appreciate autistic peers and autistic people they may work with in their future careers. Methods: We adapted an autistic-affirming training from a training developed in other cultural contexts and evaluated it with 107 university students in France using a pretest-post-test design. Results: Questionnaire responses suggested that our brief online training helped improve attitudes toward inclusion, autism knowledge, and stigma among future educators and psychologists in France. Participants' open-ended definitions of autism revealed increased alignment with the neurodiversity movement after training. Conclusions: Findings suggest that wider-scale autistic-led adaptations of autism trainings like the one described in this report could begin to ameliorate autism stigma in France.

Why is this an important issue?: Autistic people in France have been treated very badly in the past. They have been left out of school and hurt by professionals. They still face stigma. This means they are often misunderstood, made fun of, and excluded. Some are forced to take medications they do not want. Autistic people in France have been trying to help other people in France understand autism. What was the purpose of this study?: We wanted to see whether autism training could help university students in France to better understand autistic people. We wanted to see whether our training could help students appreciate autistic people more (or lower stigma). We also wanted to see whether the training could help students understand that it is important to include autistic people in classes with other students at school. What did the researchers do?: Researchers in France, Lebanon, and the United States modified an autism training that had been used in other countries. The training was autistic affirming, which means it taught people to listen to autistic people and to see their strengths. We translated it into French. We included training topics that French collaborators thought were important. We asked university students in France who were studying education and psychology to do our training online. We also asked them to fill out surveys about autism. What were the results of the study?: After doing our training, students knew more about autism than they did before training. Some learned that autism is part of a person for their whole life. They seemed to appreciate autistic people more after training. They also agreed that it is important to include autistic people in school with other students more than they had before. What do these findings add to what was already known?: This study shows that autistic-affirming training can also help people in France appreciate autistic people. Much autism training only focuses on stigma and knowledge. Our training may also have helped future educators and clinicians understand how important it is to include autistic people in school with other students. What are potential weaknesses in the study?: The students in our study were mostly women. They were all training for jobs where they can help people. We do not know whether our training would help other French people. We also cannot be sure that our training really helped the students who did it. Students may have been dishonest about how they felt about autism. In future studies, people should see whether training changes what people do, not just what they say. How will these findings help autistic adults now or in the future?: By teaching students in France about autism, we hope to begin to help make life better for autistic people in France. We hope studies like this will help people to understand autistic people better. We also hope more people conduct trainings like that used in this study around the world to improve understanding and treatment of autistic people.

Structural basis for high-order complex of SARNP and DDX39B to facilitate mRNP assembly.

mRNA in eukaryotic cells is packaged into highly compacted ribonucleoprotein particles (mRNPs) in the nucleus and exported to the cytoplasm for translation. mRNP packaging and export require the evolutionarily conserved transcription-export (TREX) complex. TREX facilitates loading of various RNA-binding proteins on mRNA through the action of its DDX39B subunit. SARNP (Tho1 [transcriptional defect of Hpr1 by overexpression 1] in yeast) is shown to interact with DDX39B and affect mRNA export. The molecular mechanism of how SARNP recognizes DDX39B and functions in mRNP assembly is unclear. Here, we determine the crystal structure of a Tho1/DDX39B/RNA complex, revealing a multivalent interaction mediated by tandem DDX39B interacting motifs in SARNP/Tho1. The high-order complex of SARNP and DDX39B is evolutionarily conserved, and human SARNP can engage with five DDX39B molecules. RNA sequencing (RNA-seq) from SARNP knockdown cells shows the most affected RNAs in export are GC rich. Our work suggests the role of the high-order SARNP/DDX39B/RNA complex in mRNP assembly and export.

Influenza virus mRNAs encode determinants for nuclear export via the cellular TREX-2 complex.

Nuclear export of influenza A virus (IAV) mRNAs occurs through the nuclear pore complex (NPC). Using the Auxin-Induced Degron (AID) system to rapidly degrade proteins, we show that among the nucleoporins localized at the nucleoplasmic side of the NPC, TPR is the key nucleoporin required for nuclear export of influenza virus mRNAs. TPR recruits the TRanscription and EXport complex (TREX)-2 to the NPC for exporting a subset of cellular mRNAs. By degrading components of the TREX-2 complex (GANP, Germinal-center Associated Nuclear Protein; PCID2, PCI domain containing 2), we show that influenza mRNAs require the TREX-2 complex for nuclear export and replication. Furthermore, we found that cellular mRNAs whose export is dependent on GANP have a small number of exons, a high mean exon length, long 3' UTR, and low GC content. Some of these features are shared by influenza virus mRNAs. Additionally, we identified a 45 nucleotide RNA signal from influenza virus HA mRNA that is sufficient to mediate GANP-dependent mRNA export. Thus, we report a role for the TREX-2 complex in nuclear export of influenza mRNAs and identified RNA determinants associated with the TREX-2-dependent mRNA export.

Alternative splicing of HDAC7 regulates its interaction with 14-3-3 proteins to alter histone marks and target gene expression.

Chromatin regulation and alternative splicing are both critical mechanisms guiding gene expression. Studies have demonstrated that histone modifications can influence alternative splicing decisions, but less is known about how alternative splicing may impact chromatin. Here, we demonstrate that several genes encoding histone-modifying enzymes are alternatively spliced downstream of T cell signaling pathways, including HDAC7, a gene previously implicated in controlling gene expression and differentiation in T cells. Using CRISPR-Cas9 gene editing and cDNA expression, we show that differential inclusion of HDAC7 exon 9 controls the interaction of HDAC7 with protein chaperones, resulting in changes to histone modifications and gene expression. Notably, the long isoform, which is induced by the RNA-binding protein CELF2, promotes expression of several critical T cell surface proteins including CD3, CD28, and CD69. Thus, we demonstrate that alternative splicing of HDAC7 has a global impact on histone modification and gene expression that contributes to T cell development.

A Bayesian model for unsupervised detection of RNA splicing based subtypes in cancers.

Identification of cancer sub-types is a pivotal step for developing personalized treatment. Specifically, sub-typing based on changes in RNA splicing has been motivated by several recent studies. We thus develop CHESSBOARD, an unsupervised algorithm tailored for RNA splicing data that captures "tiles" in the data, defined by a subset of unique splicing changes in a subset of patients. CHESSBOARD allows for a flexible number of tiles, accounts for uncertainty of splicing quantification, and is able to model missing values as additional signals. We first apply CHESSBOARD to synthetic data to assess its domain specific modeling advantages, followed by analysis of several leukemia datasets. We show detected tiles are reproducible in independent studies, investigate their possible regulatory drivers and probe their relation to known AML mutations. Finally, we demonstrate the potential clinical utility of CHESSBOARD by supplementing mutation based diagnostic assays with discovered splicing profiles to improve drug response correlation.

A systematic review and meta-analysis of associations between primarily non-autistic people's characteristics and attitudes toward autistic people.

This systematic review includes a narrative synthesis and meta-analysis of research on the associations between primarily non-autistic people's characteristics and their attitudes toward autistic people. Of 47 studies included in the narrative synthesis, White undergraduate students were surveyed most frequently. Demographic characteristics were the factors most frequently tested for associations with attitudes, followed by contact-related factors (i.e., quantity and quality), knowledge about autism, trait and personality factors, and other factors that did not fit into a single category. Internal consistency was not reported for some instruments assessing raters' characteristics; some instruments had alpha levels lower than 0.70, and many characteristics of raters were measured using one-item measures. Moreover, theoretical motivations for investigating the raters' characteristics were rarely provided. A total of 36 studies were included in the meta-analysis, which showed that attitudes toward autistic people were significantly associated with participants' gender, knowledge about autism, and quality and quantity of their previous contact with autistic people, but not with their age or autistic traits. These findings indicate a need for more studies that focus on context-related characteristics (e.g., institutional variables such as support/commitment to inclusion), use reliable instruments to measure non-autistic people's characteristics, and situate their investigation in a theoretical framework.

Explicit stigma and implicit biases toward autism in South Korea versus the United States.

LAY ABSTRACT: How people report their feelings about autism may be different from how they actually think about autism because some people may not want to reveal their true feelings. People who value the group's goal tend to present themselves as more socially acceptable than people who value one person's interests. We studied how people in South Korea and the United States report their feelings about autism and think about autism. Koreans tend to value the group's goals. Americans tend to prefer one person's goals. Koreans reported that they wanted more space from autistic people than Americans did. Koreans were more likely to think about autism with negative words (and think more negatively about autism). How Koreans and Americans report their feelings about autism was not related to their thoughts about autism. People who knew about autism and liked meeting with autistic people wanted to get closer to autistic people in South Korea and the US, Koreans who had met autistic people and thought that people who newly came to Korea from abroad should be more like Koreans did not want to get very close to autistic people. This could be because very few foreign people live in South Korea compared to the United States. Teaching Koreans that all cultures have values and should be appreciated will help them like autistic people more.

Does learning you are autistic at a younger age lead to better adult outcomes? A participatory exploration of the perspectives of autistic university students.

LAY ABSTRACT: People learn they are autistic at different ages. We wanted to know if telling kids they are autistic earlier helps them feel better about their lives when they grow up. We are a team of autistic and non-autistic students and professors. Seventy-eight autistic university students did our online survey. They shared how they found out they were autistic and how they felt about being autistic. They also shared how they feel about their lives now. Around the same number of students learned they were autistic from doctors and parents. Students who learned they were autistic when they were younger felt happier about their lives than people who learned they were autistic when they were older. Students who learned they were autistic when they were older felt happier about being autistic when they first found out than people who did not have to wait as long. Our study shows that it is probably best to tell people they are autistic as soon as possible. The students who did our study did not think it was a good idea to wait until children are adults to tell them they are autistic. They said that parents should tell their children they are autistic in ways that help them understand and feel good about who they are.

Learning from the experts: Evaluating a participatory autism and universal design training for university educators.

LAY ABSTRACT: Autistic university students have many strengths. They also go through difficulties that professors may not understand. Professors may not understand what college life is like for autistic students. They might judge autistic students. A team of autistic and non-autistic researchers made a training to help professors understand autistic students better. This training also gave professors ideas to help them teach all of their students. Ninety-eight professors did an online survey before the autism training. They shared how they felt about autism and teaching. Before our training, professors who knew more about autism appreciated autism more. Professors who thought people should be equal and women also appreciated autism more. Then, 89 of the professors did our training and another survey after the training. This helped us see what they learned from the training. They did one more survey a month later. This helped us see what they remembered. Our training helped professors understand and value autism. It also helped them understand how they can teach all students better. The professors remembered a lot of what we taught them. This study shows that a training that autistic people helped make can help professors understand their autistic students better.

Comparing narrative writing of autistic and non-autistic College students.

We compared short stories by autistic (n = 19) and non-autistic (n = 23) university students. We used automated software and content analysis to code students' stories. We found that writings were more similar than different. However, autistic students' stories were rated at a higher reading level (p = .013) than non-autistic students'. Autistic students' stories contained fewer grammatical errors (p = .02) but were less likely to include a climax (p = .026). Autistic students reported more positive writing affect than non-autistic students (p = .026). Higher writing affect was associated with writing highly fictional texts (p = .03) that contained more sentences (p = .005). Findings suggest writing may be a strength for autistic students and opportunities to write creatively may promote positive affect toward writing.

Do Autistic People's Support Needs and Non-Autistic People's Support for the Neurodiversity Movement Contribute to Heightened Autism Stigma in South Korea vs. the US?

We examined stigma towards vignette characters representing diverse autistic characteristics (social, non-speaking, or repetitive interests or restricted behaviors; RIRB) among 259 South Korean and 240 American participants (age range = 18 ~ 74). Within each domain, participants were randomized to read a vignette depicting low or high support needs. Koreans reported greater stigma towards autistic characteristics and less awareness of and support for the neurodiversity movement than Americans. Autistic characters' support needs and rater characteristics (autism knowledge, neurodiversity endorsement, and contact quantity) predicted stigma in at least one domain, and after accounting for these variables, participants' nationality was suggestively associated only with stigma towards social characteristics and RIRB. Findings highlight the need for culturally adapted-training that provides contact with diverse autistic people.