Exon-intron architecture determines mRNA stability by dictating m6A deposition
Uzonyi, A.; Slobodin, B.; Schwartz, S.
Show abstract
N6-methyladenosine (m6A), a widespread destabilizing mark on mRNA, is non-uniformly distributed across the transcriptome, yet the basis for its selective deposition is unknown. Here, we uncover that m6A deposition is not selective. Instead, m6A distribution is exclusion-based: m6A-consensus harboring sites are methylated by default, unless they are within a window of up to [~]200 nt from an exon-intron junction. A simple model, relying exclusively on presence of m6A motifs and exon-intron architecture allows high accuracy recapitulation of experimentally-measured m6A profiles and of all m6A hallmarks. We further establish that m6A serves as the long-sought mechanism underlying the strong association between exon-intron architecture and mRNA stability. Our findings establish a mechanism by which the memory of nuclear RNA splicing is covalently etched on an mRNA, in the form of m6A, and determines its cytoplasmic stability, with broad implications on the regulation, function, and evolution of both m6A and mRNA stability.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- PYM1 limits non-canonical Exon Junction Complex occupancy in a gene architecture dependent manner to tune mRNA expression 96%
- LUC7 proteins define two major classes of 5' splice sites in animals and plants 96%
- Quantifying negative selection in human 3' UTRs uncovers constrained targets of RNA-binding proteins 96%
Similar papers in this journal
- rec-Y2H matrix screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins 96%
- Studying RNA#8211;DNA interactome by Red-C identifies noncoding RNAs associated with repressed chromatin compartment and reveals transcription dynamics 96%
- A massively parallel reporter assay reveals focused and broadly encoded RNA localization signals in neurons 96%
Similar papers in this journal
- ZC3H4 restricts non-coding transcription in human cells 96%
- Association with TFIIIC limits MYCN localization in hubs of active promoters and chromatin accumulation of non-phosphorylated RNA Polymerase II 96%
- The emergence and evolution of gene expression in genome regions replete with regulatory motifs 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.