Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 311
Filtrar
1.
Essays Biochem ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623427

RESUMO

RNA molecules have emerged as a new class of promising therapeutics to expand the range of druggable targets in the genome. In addition to 'canonical' protein-coding mRNAs, the emerging richness of sense and antisense long non-coding RNAs (lncRNAs) provides a new reservoir of molecular tools for RNA-based drugs. LncRNAs are composed of modular structural domains with specific activities involving the recruitment of protein cofactors or directly interacting with nucleic acids. A single therapeutic RNA transcript can then be assembled combining domains with defined secondary structures and functions, and antisense sequences specific for the RNA/DNA target of interest. As the first representative molecules of this new pharmacology, we have identified SINEUPs, a new functional class of natural antisense lncRNAs that increase the translation of partially overlapping mRNAs. Their activity is based on the combination of two domains: an embedded mouse inverted SINEB2 element that enhances mRNA translation (effector domain) and an overlapping antisense region that provides specificity for the target sense transcript (binding domain). By genetic engineering, synthetic SINEUPs can potentially target any mRNA of interest increasing translation and therefore the endogenous level of the encoded protein. In this review, we describe the state-of-the-art knowledge of SINEUPs and discuss recent publications showing their potential application in diseases where a physiological increase of endogenous protein expression can be therapeutic.

2.
PLoS Biol ; 19(10): e3001419, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34618807

RESUMO

Evolving in sync with the computation revolution over the past 30 years, computational biology has emerged as a mature scientific field. While the field has made major contributions toward improving scientific knowledge and human health, individual computational biology practitioners at various institutions often languish in career development. As optimistic biologists passionate about the future of our field, we propose solutions for both eager and reluctant individual scientists, institutions, publishers, funding agencies, and educators to fully embrace computational biology. We believe that in order to pave the way for the next generation of discoveries, we need to improve recognition for computational biologists and better align pathways of career success with pathways of scientific progress. With 10 outlined steps, we call on all adjacent fields to move away from the traditional individual, single-discipline investigator research model and embrace multidisciplinary, data-driven, team science.

3.
BMC Genom Data ; 22(1): 33, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521352

RESUMO

BACKGROUND: The lymphatic and the blood vasculature are closely related systems that collaborate to ensure the organism's physiological function. Despite their common developmental origin, they present distinct functional fates in adulthood that rely on robust lineage-specific regulatory programs. The recent technological boost in sequencing approaches unveiled long noncoding RNAs (lncRNAs) as prominent regulatory players of various gene expression levels in a cell-type-specific manner. RESULTS: To investigate the potential roles of lncRNAs in vascular biology, we performed antisense oligonucleotide (ASO) knockdowns of lncRNA candidates specifically expressed either in human lymphatic or blood vascular endothelial cells (LECs or BECs) followed by Cap Analysis of Gene Expression (CAGE-Seq). Here, we describe the quality control steps adopted in our analysis pipeline before determining the knockdown effects of three ASOs per lncRNA target on the LEC or BEC transcriptomes. In this regard, we especially observed that the choice of negative control ASOs can dramatically impact the conclusions drawn from the analysis depending on the cellular background. CONCLUSION: In conclusion, the comparison of negative control ASO effects on the targeted cell type transcriptomes highlights the essential need to select a proper control set of multiple negative control ASO based on the investigated cell types.

4.
Methods Mol Biol ; 2351: 67-90, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382184

RESUMO

The Cap Analysis of Gene Expression (CAGE) is a powerful method to identify Transcription Start Sites (TSSs) of capped RNAs while simultaneously measuring transcripts expression level. CAGE allows mapping at single nucleotide resolution at all active promoters and enhancers. Large CAGE datasets have been produced over the years from individual laboratories and consortia, including the Encyclopedia of DNA Elements (ENCODE) and Functional Annotation of the Mammalian Genome (FANTOM) consortia. These datasets constitute open resource for TSS annotations and gene expression analysis. Here, we provide an experimental protocol for the most recent CAGE method called Low Quantity (LQ) single strand (ss) CAGE "LQ-ssCAGE", which enables cost-effective profiling of low quantity RNA samples. LQ-ssCAGE is especially useful for samples derived from cells cultured in small volumes, cellular compartments such as nuclear RNAs or for samples from developmental stages. We demonstrate the reproducibility and effectiveness of the method by constructing 240 LQ-ssCAGE libraries from 50 ng of THP-1 cell extracted RNAs and discover lowly expressed novel enhancer and promoter-derived lncRNAs.


Assuntos
Biologia Computacional/métodos , Elementos Facilitadores Genéticos , Regiões Promotoras Genéticas , Capuzes de RNA , Sítio de Iniciação de Transcrição , Bases de Dados Genéticas , Regulação da Expressão Gênica , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Anotação de Sequência Molecular , Sequências Reguladoras de Ácido Nucleico , Reprodutibilidade dos Testes , Fluxo de Trabalho
5.
Methods Mol Biol ; 2351: 201-210, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382191

RESUMO

Regulation of gene expression is a key feature for higher eukaryotes and how chromatin topology relates to gene activation is an intense area of research. Enhancer-promoter interactions are believed to mediate activation of target genes. Bidirectional transcription represents one hallmark of active enhancers that can be measured using transcriptome technologies such as Cap analysis of gene expression (CAGE). Recently, we have developed RNA and DNA interacting complexes ligated and sequenced (RADICL-Seq) a novel methodology to map genome-wide RNA-chromatin interactions in intact nuclei. Here, we describe how CAGE and RADICL-Seq data can be used to characterize enhancer elements and identify their target genes.


Assuntos
Biologia Computacional/métodos , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica , Regiões Promotoras Genéticas , Capuzes de RNA , Algoritmos , Cromatina/genética , Bases de Dados Genéticas , Sequenciamento de Nucleotídeos em Larga Escala , Sítio de Iniciação de Transcrição , Transcrição Genética , Ativação Transcricional , Transcriptoma
6.
Nat Commun ; 12(1): 3297, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078885

RESUMO

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.


Assuntos
Repetições de Microssatélites , Redes Neurais de Computação , Doenças Neurodegenerativas/genética , Sítio de Iniciação de Transcrição , Iniciação da Transcrição Genética , Células A549 , Animais , Sequência de Bases , Biologia Computacional/métodos , Aprendizado Profundo , Elementos Facilitadores Genéticos , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Camundongos , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/metabolismo , Polimorfismo Genético , Regiões Promotoras Genéticas
7.
Genome Res ; 31(6): 995-1010, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33795334

RESUMO

Long noncoding RNAs or lncRNAs are a class of non-protein-coding RNAs that are >200 nt in length. Almost 50% of lncRNAs during zebrafish development are transcribed in an antisense direction to a protein-coding gene. However, the role of these natural antisense transcripts (NATs) during development remains enigmatic. To understand NATs in early vertebrate development, we took a computational biology approach and analyzed existing as well as novel data sets. Our analysis indicates that zebrafish NATs can be divided into two major classes based on their coexpression patterns with respect to the overlapping protein-coding genes. Group 1 NATs have characteristics similar to maternally deposited RNAs in that their levels decrease as development progresses. Group 1 NAT levels are negatively correlated with that of overlapping sense-strand protein-coding genes. Conversely, Group 2 NATs are coexpressed with overlapping protein-coding genes. In contrast to Group 1, which is enriched in genes involved in developmental pathways, Group 2 protein-coding genes are enriched in housekeeping functions. Group 1 NATs also show larger overlap and higher complementarity with the sense-strand mRNAs compared to other NATs. In addition, our transcriptomics data, quantifying RNA levels from cytoplasmic and nuclear compartments, indicates that Group 1 NATs are more abundant in the cytosol. Based on their expression pattern, cytosolic nature, and their higher complementarity to the overlapping developmental mRNAs, we speculate that Group 1 NATs function post-transcriptionally to silence spurious expression of developmental genes.

8.
Stem Cell Reports ; 16(4): 810-824, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33711266

RESUMO

Cellular reprogramming is driven by a defined set of transcription factors; however, the regulatory logic that underlies cell-type specification and diversification remains elusive. Single-cell RNA-seq provides unprecedented coverage to measure dynamic molecular changes at the single-cell resolution. Here, we multiplex and ectopically express 20 pro-neuronal transcription factors in human dermal fibroblasts and demonstrate a widespread diversification of neurons based on cell morphology and canonical neuronal marker expressions. Single-cell RNA-seq analysis reveals diverse and distinct neuronal subtypes, including reprogramming processes that strongly correlate with the developing brain. Gene mapping of 20 exogenous pro-neuronal transcription factors further unveiled key determinants responsible for neuronal lineage specification and a regulatory logic dictating neuronal diversification, including glutamatergic and cholinergic neurons. The multiplex scRNA-seq approach is a robust and scalable approach to elucidate lineage and cellular specification across various biological systems.

9.
Nat Commun ; 12(1): 925, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568674

RESUMO

Recent studies have revealed the importance of long noncoding RNAs (lncRNAs) as tissue-specific regulators of gene expression. There is ample evidence that distinct types of vasculature undergo tight transcriptional control to preserve their structure, identity, and functions. We determine a comprehensive map of lineage-specific lncRNAs in human dermal lymphatic and blood vascular endothelial cells (LECs and BECs), combining RNA-Seq and CAGE-Seq. Subsequent antisense oligonucleotide-knockdown transcriptomic profiling of two LEC- and two BEC-specific lncRNAs identifies LETR1 as a critical gatekeeper of the global LEC transcriptome. Deep RNA-DNA, RNA-protein interaction studies, and phenotype rescue analyses reveal that LETR1 is a nuclear trans-acting lncRNA modulating, via key epigenetic factors, the expression of essential target genes, including KLF4 and SEMA3C, governing the growth and migratory ability of LECs. Together, our study provides several lines of evidence supporting the intriguing concept that every cell type expresses precise lncRNA signatures to control lineage-specific regulatory programs.


Assuntos
Células Endoteliais/citologia , Fatores de Transcrição Kruppel-Like/metabolismo , Semaforinas/metabolismo , Movimento Celular , Proliferação de Células , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Humanos , Fatores de Transcrição Kruppel-Like/genética , RNA Longo não Codificante , Semaforinas/genética
10.
Nucleic Acids Res ; 49(D1): D892-D898, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33211864

RESUMO

The Functional ANnoTation Of the Mammalian genome (FANTOM) Consortium has continued to provide extensive resources in the pursuit of understanding the transcriptome, and transcriptional regulation, of mammalian genomes for the last 20 years. To share these resources with the research community, the FANTOM web-interfaces and databases are being regularly updated, enhanced and expanded with new data types. In recent years, the FANTOM Consortium's efforts have been mainly focused on creating new non-coding RNA datasets and resources. The existing FANTOM5 human and mouse miRNA atlas was supplemented with rat, dog, and chicken datasets. The sixth (latest) edition of the FANTOM project was launched to assess the function of human long non-coding RNAs (lncRNAs). From its creation until 2020, FANTOM6 has contributed to the research community a large dataset generated from the knock-down of 285 lncRNAs in human dermal fibroblasts; this is followed with extensive expression profiling and cellular phenotyping. Other updates to the FANTOM resource includes the reprocessing of the miRNA and promoter atlases of human, mouse and chicken with the latest reference genome assemblies. To facilitate the use and accessibility of all above resources we further enhanced FANTOM data viewers and web interfaces. The updated FANTOM web resource is publicly available at https://fantom.gsc.riken.jp/.


Assuntos
Anotação de Sequência Molecular , RNA Longo não Codificante/genética , Transcriptoma/genética , Animais , Sítios de Ligação , Cromatina/metabolismo , Drosophila/genética , Fibroblastos/citologia , Fibroblastos/metabolismo , Genoma , Humanos , Metadados , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Regiões Promotoras Genéticas , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismo , Interface Usuário-Computador
11.
Nucleic Acids Res ; 48(20): 11626-11644, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33130894

RESUMO

SINEUPs are long non-coding RNAs (lncRNAs) that contain a SINE element, and which up-regulate the translation of target mRNA. They have been studied in a wide range of applications, as both biological and therapeutic tools, although the underpinning molecular mechanism is unclear. Here, we focused on the sub-cellular distribution of target mRNAs and SINEUP RNAs, performing co-transfection of expression vectors for these transcripts into human embryonic kidney cells (HEK293T/17), to investigate the network of translational regulation. The results showed that co-localization of target mRNAs and SINEUP RNAs in the cytoplasm was a key phenomenon. We identified PTBP1 and HNRNPK as essential RNA binding proteins. These proteins contributed to SINEUP RNA sub-cellular distribution and to assembly of translational initiation complexes, leading to enhanced target mRNA translation. These findings will promote a better understanding of the mechanisms employed by regulatory RNAs implicated in efficient protein translation.


Assuntos
Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Iniciação Traducional da Cadeia Peptídica , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , RNA Longo não Codificante/metabolismo , Citoplasma/metabolismo , Proteínas de Fluorescência Verde/análise , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Células HEK293 , Humanos , Proteínas de Ligação a RNA/metabolismo
12.
BMC Genomics ; 21(1): 766, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148170

RESUMO

BACKGROUND: Protein Disulfide Isomerases are thiol oxidoreductase chaperones from thioredoxin superfamily with crucial roles in endoplasmic reticulum proteostasis, implicated in many diseases. The family prototype PDIA1 is also involved in vascular redox cell signaling. PDIA1 is coded by the P4HB gene. While forced changes in P4HB gene expression promote physiological effects, little is known about endogenous P4HB gene regulation and, in particular, gene modulation by alternative splicing. This study addressed the P4HB splice variant landscape. RESULTS: Ten protein coding sequences (Ensembl) of the P4HB gene originating from alternative splicing were characterized. Structural features suggest that except for P4HB-021, other splice variants are unlikely to exert thiol isomerase activity at the endoplasmic reticulum. Extensive analyses using FANTOM5, ENCODE Consortium and GTEx project databases as RNA-seq data sources were performed. These indicated widespread expression but significant variability in the degree of isoform expression among distinct tissues and even among distinct locations of the same cell, e.g., vascular smooth muscle cells from different origins. P4HB-02, P4HB-027 and P4HB-021 were relatively more expressed across each database, the latter particularly in vascular smooth muscle. Expression of such variants was validated by qRT-PCR in some cell types. The most consistently expressed splice variant was P4HB-021 in human mammary artery vascular smooth muscle which, together with canonical P4HB gene, had its expression enhanced by serum starvation. CONCLUSIONS: Our study details the splice variant landscape of the P4HB gene, indicating their potential role to diversify the functional reach of this crucial gene. P4HB-021 splice variant deserves further investigation in vascular smooth muscle cells.


Assuntos
Pró-Colágeno-Prolina Dioxigenase , Isomerases de Dissulfetos de Proteínas , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Humanos , Mutação , Pró-Colágeno-Prolina Dioxigenase/genética , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Isomerases de Dissulfetos de Proteínas/genética , Transdução de Sinais
13.
FEBS Lett ; 594(24): 4357-4369, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33012004

RESUMO

Chemically modified mRNAs are extensively studied with a view toward their clinical application. In particular, long noncoding RNAs (lncRNAs) containing SINE elements, which enhance the translation of their target mRNAs (i.e., SINEUPs), have potential as RNA therapies for various diseases, such as haploinsufficiencies. To establish a SINEUP-based system for efficient protein expression, we directly transfected chemically modified in vitro transcribed (mIVT) SINEUP RNAs to examine their effects on target mRNA translation. mIVT SINEUP RNAs enhanced translation of EGFP mRNA and endogenous target Sox9 mRNA in both cultured cells and a cell-free translation system. Our findings reveal the functional role of RNA modifications in SINEUPs and suggest several broad clinical applications of such an RNA regulatory system.


Assuntos
Biossíntese de Proteínas , RNA Longo não Codificante/química , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Células HEK293 , Células Hep G2 , Humanos , Técnicas In Vitro , Estabilidade de RNA , RNA Longo não Codificante/síntese química , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição SOX9/biossíntese , Fatores de Transcrição SOX9/genética , Regulação para Cima
14.
Sci Rep ; 10(1): 17991, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093512

RESUMO

Transcription of human papillomavirus (HPV) genes proceeds unidirectionally from multiple promoters. Direct profiling of transcription start sites (TSSs) by Cap Analysis Gene Expression (CAGE) is a powerful strategy for examining individual HPV promoter activity. The objective of this study was to evaluate alterations of viral promoter activity during infection using CAGE technology. We used CAGE-based sequencing of 46 primary cervical samples, and quantitatively evaluated TSS patterns in the HPV transcriptome at a single-nucleotide resolution. TSS patterns were classified into two types: early promoter-dominant type (Type A) and late promoter-dominant type (Type B). The Type B pattern was more frequently found in CIN1 and CIN2 lesions than in CIN3 and cancer samples. We detected transcriptomes from multiple HPV types in five samples. Interestingly, in each sample, the TSS patterns of both HPV types were the same. The viral gene expression pattern was determined by the differentiation status of the epithelial cells, regardless of HPV type. We performed unbiased analyses of TSSs across the HPV genome in clinical samples. Visualising TSS pattern dynamics, including TSS shifts, provides new insights into how HPV infection status relates to disease state.


Assuntos
Alphapapillomavirus/genética , Colo do Útero/patologia , Regulação Viral da Expressão Gênica , Infecções por Papillomavirus/complicações , Regiões Promotoras Genéticas , Capuzes de RNA/genética , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Alphapapillomavirus/isolamento & purificação , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/genética , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Sítio de Iniciação de Transcrição , Transcrição Genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Proteínas Virais/genética
16.
Genome Res ; 30(7): 951-961, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32718981

RESUMO

Gene expression profiles in homologous tissues have been observed to be different between species, which may be due to differences between species in the gene expression program in each cell type, but may also reflect differences in cell type composition of each tissue in different species. Here, we compare expression profiles in matching primary cells in human, mouse, rat, dog, and chicken using Cap Analysis Gene Expression (CAGE) and short RNA (sRNA) sequencing data from FANTOM5. While we find that expression profiles of orthologous genes in different species are highly correlated across cell types, in each cell type many genes were differentially expressed between species. Expression of genes with products involved in transcription, RNA processing, and transcriptional regulation was more likely to be conserved, while expression of genes encoding proteins involved in intercellular communication was more likely to have diverged during evolution. Conservation of expression correlated positively with the evolutionary age of genes, suggesting that divergence in expression levels of genes critical for cell function was restricted during evolution. Motif activity analysis showed that both promoters and enhancers are activated by the same transcription factors in different species. An analysis of expression levels of mature miRNAs and of primary miRNAs identified by CAGE revealed that evolutionary old miRNAs are more likely to have conserved expression patterns than young miRNAs. We conclude that key aspects of the regulatory network are conserved, while differential expression of genes involved in cell-to-cell communication may contribute greatly to phenotypic differences between species.

17.
Nature ; 583(7818): 685-686, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32728235
18.
Nucleic Acids Res ; 48(16): 9346-9360, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32697302

RESUMO

Long non-coding RNAs (lncRNAs) are attracting widespread attention for their emerging regulatory, transcriptional, epigenetic, structural and various other functions. Comprehensive transcriptome analysis has revealed that retrotransposon elements (REs) are transcribed and enriched in lncRNA sequences. However, the functions of lncRNAs and the molecular roles of the embedded REs are largely unknown. The secondary and tertiary structures of lncRNAs and their embedded REs are likely to have essential functional roles, but experimental determination and reliable computational prediction of large RNA structures have been extremely challenging. We report here the nuclear magnetic resonance (NMR)-based secondary structure determination of the 167-nt inverted short interspersed nuclear element (SINE) B2, which is embedded in antisense Uchl1 lncRNA and upregulates the translation of sense Uchl1 mRNAs. By using NMR 'fingerprints' as a sensitive probe in the domain survey, we successfully divided the full-length inverted SINE B2 into minimal units made of two discrete structured domains and one dynamic domain without altering their original structures after careful boundary adjustments. This approach allowed us to identify a structured domain in nucleotides 31-119 of the inverted SINE B2. This approach will be applicable to determining the structures of other regulatory lncRNAs.


Assuntos
Conformação de Ácido Nucleico , RNA Longo não Codificante/ultraestrutura , Retroelementos/genética , Elementos Nucleotídeos Curtos e Dispersos/genética , Biologia Computacional , Humanos , Espectroscopia de Ressonância Magnética , RNA Antissenso/genética , RNA Antissenso/ultraestrutura , RNA Longo não Codificante/genética , Transcriptoma/genética , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/ultraestrutura
19.
Cell ; 181(3): 512-514, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32359433

RESUMO

Guo and colleagues discover a new layer of complexity to the lncRNA evolution where positionally conserved lncRNAs in human ESCs are broadly spliced and exported to the cytoplasm contrary to their mouse counterpart that are predominantly unspliced and nuclear retained. Distinct processing leads to species-specific lncRNA function in pluripotency maintenance.


Assuntos
RNA Longo não Codificante , Animais , Núcleo Celular , Citoplasma , Humanos , Camundongos , RNA Longo não Codificante/genética , Células-Tronco
20.
Noncoding RNA ; 6(2)2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32471183

RESUMO

An increasing number of studies have revealed that long non-coding RNAs (lncRNAs) play important roles in gene regulation and nuclear organization. Although the mechanisms are still largely unknown, many lncRNAs have been shown to interact with chromatin. Thus, one approach to understanding the function of these lncRNAs is to identify their sites of genomic interaction. Hybridization capture methods using oligonucleotide probes have been used for years to study chromatin-associated RNA. Recently, several groups have developed novel methods based on proximity ligation to investigate RNA-chromatin interactions at a genome-wide scale. This review discusses these technologies and highlights their advantages and disadvantages for the consideration of potential users.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...