Cis-element acquisition converts pervasive transcripts into translated mRNAs
- 1Tsinghua University
Abstract
Mammalian genomes produce many unstable non-coding transcripts (e.g., PROMPTs and eRNAs) that are rapidly degraded by the nuclear exosome. This study tests whether adding splicing and polyadenylation signals to endogenous non-coding loci can convert them into stable mRNAs. Using CRISPR-Cas9 knock-in in murine cancer cells, the authors show that both signals together render transcripts stable, polyadenylated, exported, and translated into protein. Quantitatively, polyadenylation extends half-life from ~20 minutes to ~12 hours, while splicing primarily drives nuclear export, with export efficiency predicting protein output. Interestingly, untranslated regions of naturally intronless genes can substitute for splicing, mainly by enhancing export. A genome-wide CRISPR screen implicates export, processing, and translation factors such as NXF1, PABPN1, and EIF3G in this conversion. Overall, defined cis-elements suffice to transform pervasive transcripts into functional mRNAs, with nuclear export as the key rate-limiting step. This provides experimental evidence for a potential evolutionary path by which non-coding loci can be co-opted into the coding genome.
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BibTeX
@misc{david2026ciselement,
title = {{Cis-element acquisition converts pervasive transcripts into translated mRNAs}},
author = {C. J. David and R. Zhang},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.749023},
url = {https://www.biorxiv.org/content/10.64898/2026.09.02.749023v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Cis-element acquisition converts pervasive transcripts into translated mRNAs
AU - C. J. David
AU - R. Zhang
PY - 2026
DA - 2026/09/02
PB - bioRxiv
DO - 10.64898/2026.09.02.749023
UR - https://www.biorxiv.org/content/10.64898/2026.09.02.749023v1
AB - Mammalian genomes produce many unstable non-coding transcripts (e.g., PROMPTs and eRNAs) that are rapidly degraded by the nuclear exosome. This study tests whether adding splicing and polyadenylation signals to endogenous non-coding loci can convert them into stable mRNAs. Using CRISPR-Cas9 knock-in in murine cancer cells, the authors show that both signals together render transcripts stable, polyadenylated, exported, and translated into protein. Quantitatively, polyadenylation extends half-life from ~20 minutes to ~12 hours, while splicing primarily drives nuclear export, with export efficiency predicting protein output. Interestingly, untranslated regions of naturally intronless genes can substitute for splicing, mainly by enhancing export. A genome-wide CRISPR screen implicates export, processing, and translation factors such as NXF1, PABPN1, and EIF3G in this conversion. Overall, defined cis-elements suffice to transform pervasive transcripts into functional mRNAs, with nuclear export as the key rate-limiting step. This provides experimental evidence for a potential evolutionary path by which non-coding loci can be co-opted into the coding genome.
ER -