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Neighborhood regulation by lncRNA promoters, transcription, and splicing

Jesse M. Engreitz, Jenna E. Haines, Glen Munson, Jenny Chen, Elizabeth M. Perez, Michael Kane, Patrick E. McDonel, Mitchell Guttman, Eric S. Lander
doi: https://doi.org/10.1101/050948
Jesse M. Engreitz
1Broad Institute of Harvard and MIT, Cambridge MA 02142
2Division of Health Sciences and Technology, MIT, Cambridge MA 02139
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Jenna E. Haines
1Broad Institute of Harvard and MIT, Cambridge MA 02142
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Glen Munson
1Broad Institute of Harvard and MIT, Cambridge MA 02142
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Jenny Chen
1Broad Institute of Harvard and MIT, Cambridge MA 02142
2Division of Health Sciences and Technology, MIT, Cambridge MA 02139
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Elizabeth M. Perez
1Broad Institute of Harvard and MIT, Cambridge MA 02142
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Michael Kane
1Broad Institute of Harvard and MIT, Cambridge MA 02142
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Patrick E. McDonel
1Broad Institute of Harvard and MIT, Cambridge MA 02142
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Mitchell Guttman
3Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125
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Eric S. Lander
1Broad Institute of Harvard and MIT, Cambridge MA 02142
4Department of Biology, MIT, Cambridge MA 02139
5Department of Systems Biology, Harvard Medical School, Boston MA 02114
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  • For correspondence: eric@broadinstitute.org
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Abstract

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 29, 2016.
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Neighborhood regulation by lncRNA promoters, transcription, and splicing
Jesse M. Engreitz, Jenna E. Haines, Glen Munson, Jenny Chen, Elizabeth M. Perez, Michael Kane, Patrick E. McDonel, Mitchell Guttman, Eric S. Lander
bioRxiv 050948; doi: https://doi.org/10.1101/050948
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Neighborhood regulation by lncRNA promoters, transcription, and splicing
Jesse M. Engreitz, Jenna E. Haines, Glen Munson, Jenny Chen, Elizabeth M. Perez, Michael Kane, Patrick E. McDonel, Mitchell Guttman, Eric S. Lander
bioRxiv 050948; doi: https://doi.org/10.1101/050948

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