Differing genetics of saline and cocaine self-administration in the hybrid mouse diversity panel.

To identify genes involved in regulating the behavioral and brain transcriptomic response to the potentially addictive drug cocaine, we performed genome-wide association studies (GWASs) for intravenous self-administration of cocaine or saline (as a control) over 10 days using a panel of inbred and recombinant inbred mice. A linear mixed model increased statistical power for these longitudinal data and identified 145 loci for responding when saline only was delivered, compared to 17 for the corresponding cocaine GWAS. Only one locus overlapped.

hnRNPM protects against the dsRNA-mediated interferon response by repressing LINE-associated cryptic splicing.

RNA splicing is pivotal in post-transcriptional gene regulation, yet the exponential expansion of intron length in humans poses a challenge for accurate splicing. Here, we identify hnRNPM as an essential RNA-binding protein that suppresses cryptic splicing through binding to deep introns, maintaining human transcriptome integrity. Long interspersed nuclear elements (LINEs) in introns harbor numerous pseudo splice sites.

Genetic pathways regulating the longitudinal acquisition of cocaine self-administration in a panel of inbred and recombinant inbred mice.

To identify addiction genes, we evaluate intravenous self-administration of cocaine or saline in 84 inbred and recombinant inbred mouse strains over 10 days. We integrate the behavior data with brain RNA-seq data from 41 strains. The self-administration of cocaine and that of saline are genetically distinct.

LINE-associated cryptic splicing induces dsRNA-mediated interferon response and tumor immunity.

RNA splicing plays a critical role in post-transcriptional gene regulation. Exponential expansion of intron length poses a challenge for accurate splicing. Little is known about how cells prevent inadvertent and often deleterious expression of intronic elements due to cryptic splicing.

Rrp6 Moonlights in an RNA Exosome-Independent Manner to Promote Cell Survival and Gene Expression during Stress.

The nuclear RNA exosome is essential for RNA processing and degradation. Here, we show that the exosome nuclear-specific subunit Rrp6p promotes cell survival during heat stress through the cell wall integrity (CWI) pathway, independently of its catalytic activity or association with the core exosome. Rrp6p exhibits negative genetic interactions with the Slt2/Mpk1p or Paf1p elongation factors required for expression of CWI genes during stress.