Hedonic eating, obesity, and addiction result from increased neuropeptide Y in the nucleus accumbens during human brain evolution.

The nucleus accumbens (NAc) is central to motivation and action, exhibiting one of the highest densities of neuropeptide Y (NPY) in the brain. Within the NAc, NPY plays a role in reward and is involved in emotional behavior and in increasing alcohol and drug addiction and fat intake. Here, we examined NPY innervation and neurons of the NAc in humans and other anthropoid primates in order to determine whether there are differences among these various species that would correspond to behavioral or life history variables. We quantified NPY-immunoreactive axons and neurons in the NAc of 13 primate species, including humans, great apes, and monkeys. Our data show that the human brain is unique among primates in having denser NPY innervation within the NAc, as measured by axon length density to neuron density, even after accounting for brain size. Combined with our previous finding of increased dopaminergic innervation in the same region, our results suggest that the neurochemical profile of the human NAc appears to have rendered our species uniquely susceptible to neurophysiological conditions such as addiction. The increase in NPY specific to the NAc may represent an adaptation that favors fat intake and contributes to an increased vulnerability to eating disorders, obesity, as well as alcohol and drug dependence. Along with our findings for dopamine, these deeply rooted structural attributes of the human brain are likely to have emerged early in the human clade, laying the groundwork for later brain expansion and the development of cognitive and behavioral specializations.

Dynamically expressed small RNAs, substantially driven by genomic structural variants, contribute to transcriptomic changes during tomato domestication.

Tomato has undergone extensive selections during domestication. Recent progress has shown that genomic structural variants (SVs) have contributed to gene expression dynamics during tomato domestication, resulting in changes of important traits. Here, we performed comprehensive analyses of small RNAs (sRNAs) from nine representative tomato accessions. We demonstrate that SVs substantially contribute to the dynamic expression of the three major classes of plant sRNAs: microRNAs (miRNAs), phased secondary short interfering RNAs (phasiRNAs), and 24-nucleotide heterochromatic siRNAs (hc-siRNAs). Changes in the abundance of phasiRNAs and 24-nucleotide hc-siRNAs likely contribute to the alteration of mRNA gene expression in cis during tomato domestication, particularly for genes associated with biotic and abiotic stress tolerance. We also observe that miRNA expression dynamics are associated with imprecise processing, alternative miRNA-miRNA* selections, and SVs. SVs mainly affect the expression of less-conserved miRNAs that do not have established regulatory functions or low abundant members in highly expressed miRNA families. Our data highlight different selection pressures on miRNAs compared to phasiRNAs and 24-nucleotide hc-siRNAs. Our findings provide insights into plant sRNA evolution as well as SV-based gene regulation during crop domestication. Furthermore, our dataset provides a rich resource for mining the sRNA regulatory network in tomato.

Potato Spindle Tuber Viroid Modulates Its Replication through a Direct Interaction with a Splicing Regulator.

Viroids are circular noncoding RNAs (ncRNAs) that infect plants. Despite differences in the genetic makeup and biogenesis, viroids and various long ncRNAs all rely on RNA structure-based interactions with cellular factors for function. Viroids replicating in the nucleus utilize DNA-dependent RNA polymerase II for transcription, a process that involves a unique splicing form of transcription factor IIIA (TFIIIA-7ZF). Here, we provide evidence showing that potato spindle tuber viroid (PSTVd) interacts with a TFIIIA splicing regulator (ribosomal protein L5 [RPL5]) in vitro and in vivo PSTVd infection compromises the regulatory role of RPL5 over splicing of TFIIIA transcripts, while ectopic expression of RPL5 reduces TFIIIA-7ZF expression and attenuates PSTVd accumulation. Furthermore, we illustrate that the RPL5 binding site on the PSTVd genome resides in the central conserved region critical for replication. Together, our data suggest that viroids can regulate their own replication and modulate specific regulatory factors leading to splicing changes in only one or a few genes. This study also has implications for understanding the functional mechanisms of ncRNAs and elucidating the global splicing changes in various host-pathogen interactions.IMPORTANCE Viroids are the smallest replicons among all living entities. As circular noncoding RNAs, viroids can replicate and spread in plants, often resulting in disease symptoms. Potato spindle tuber viroid (PSTVd), the type species of nuclear-replicating viroids, requires a unique splicing form of transcription factor IIIA (TFIIIA-7ZF) for its propagation. Here, we provide evidence showing that PSTVd directly interacts with a splicing regulator, RPL5, to favor the expression of TFIIIA-7ZF, thereby promoting viroid replication. This finding provides new insights to better understand viroid biology and sheds light on the noncoding RNA-based regulation of splicing. Our discovery also establishes RPL5 as a novel negative factor regulating viroid replication in the nucleus and highlights a potential means for viroid control.

Analysis on RNA Motif-Based RNA Trafficking in Plants.

Systemic RNA trafficking widely exists in plants and is critical for integrating the healthy development and responses to environmental cues. Viroids, single-stranded circular noncoding RNAs that infect plants, have been used as a model to delineate the mechanism underlying systemic RNA trafficking. Recent work on viroids has shown that structural motifs are critical to direct RNA trafficking through distinct cellular boundaries. Here, we describe the methods for generating mutational variants using site-directed mutagenesis and infection assays to unravel the function of RNA motifs. This approach can be modified to study other RNA motif-based biological processes.