PT  - JOURNAL ARTICLE
AU  - Jesse M. Engreitz
AU  - Jenna E. Haines
AU  - Glen Munson
AU  - Jenny Chen
AU  - Elizabeth M. Perez
AU  - Michael Kane
AU  - Patrick E. McDonel
AU  - Mitchell Guttman
AU  - Eric S. Lander
TI  - Neighborhood regulation by lncRNA promoters, transcription, and splicing
AID  - 10.1101/050948
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 050948
4099  - http://biorxiv.org/content/early/2016/04/28/050948.short
4100  - http://biorxiv.org/content/early/2016/04/28/050948.full
AB  - Mammalian genomes are pervasively transcribed to produce thousands of spliced long noncoding RNAs (lncRNAs), whose functions remain poorly understood. Because recent evidence has implicated several specific lncRNA loci in the local regulation of gene expression, we sought to determine whether such local regulation is a property of many lncRNA loci. We used genetic manipulations to dissect 12 genomic loci that produce lncRNAs and found that 5 of these loci influence the expression of a neighboring gene in cis. Surprisingly, however, none of these effects required the specific lncRNA transcripts themselves and instead involved general processes associated with their production, including enhancer-like activity of gene promoters, the process of transcription, and the splicing of the transcript. Interestingly, such effects are not limited to lncRNA loci: we found similar effects on local gene expression at 4 of 6 protein-coding loci. These results demonstrate that ‘crosstalk’ among neighboring genes is a prevalent phenomenon that can involve multiple mechanisms and cis regulatory signals, including a novel role for RNA splicing. These mechanisms may explain the function and evolution of some genomic loci that produce lncRNAs.