PYM1 limits non-canonical Exon Junction Complex occupancy in a gene architecture dependent manner to tune mRNA expression

Manu Sanjeev, Lauren A. Woodward, Michael L. Schiff, Robert D. Patton, Sean Myers, Debadrita Paul, Ralf Bundschuh and Guramrit Singh ()
Additional contact information
Manu Sanjeev: The Ohio State University
Lauren A. Woodward: The Ohio State University
Michael L. Schiff: The Ohio State University
Robert D. Patton: The Ohio State University
Sean Myers: The Ohio State University
Debadrita Paul: The Ohio State University
Ralf Bundschuh: The Ohio State University
Guramrit Singh: The Ohio State University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract The Exon Junction Complex (EJC) decorates RNA exon-exon junctions and modulates mRNA fate at multiple post-transcriptional steps until its disassembly during translation. Our investigation of the EJC disassembly factor PYM1 in human embryonic kidney 293 (HEK293) cells show that the EJC-PYM1 interaction is required for translation-independent EJC destabilization but not for translation-dependent disassembly. Surprisingly, PYM1 interaction deficient EJCs are enriched on locations away from canonical EJC binding site, particularly on transcripts with no or few introns. Such non-canonical EJCs are capable of inducing nonsense-mediated mRNA decay when present downstream of stop codons. Suppression of PYM1 in human cells, including by previously reported PYM1-flavivirus capsid protein interaction, stabilizes mRNAs with fewer and longer exons that localize to endoplasmic reticulum associated TIS-granules. In summary, PYM1 limits non-canonical EJC and thereby acts as an EJC specificity factor that is hijacked by flaviviruses to reshape host cell mRNA regulation.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-63455-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63455-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-63455-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().