Back to Search Start Over

PABPN1 prevents the nuclear export of an unspliced RNA with a constitutive transport element and controls human gene expression via intron retention.

Authors :
Kwiatek L
Landry-Voyer AM
Latour M
Yague-Sanz C
Bachand F
Source :
RNA (New York, N.Y.) [RNA] 2023 May; Vol. 29 (5), pp. 644-662. Date of Electronic Publication: 2023 Feb 08.
Publication Year :
2023

Abstract

Intron retention is a type of alternative splicing where one or more introns remain unspliced in a polyadenylated transcript. Although many viral systems are known to translate proteins from mRNAs with retained introns, restriction mechanisms generally prevent export and translation of incompletely spliced mRNAs. Here, we provide evidence that the human nuclear poly(A)-binding protein, PABPN1, functions in such restrictions. Using a reporter construct in which nuclear export of an incompletely spliced mRNA is enhanced by a viral constitutive transport element (CTE), we show that PABPN1 depletion results in a significant increase in export and translation from the unspliced CTE-containing transcript. Unexpectedly, we find that inactivation of poly(A)-tail exosome targeting by depletion of PAXT components had no effect on export and translation of the unspliced reporter mRNA, suggesting a mechanism largely independent of nuclear RNA decay. Interestingly, a PABPN1 mutant selectively defective in stimulating poly(A) polymerase elongation strongly enhanced the expression of the unspliced, but not of intronless, reporter transcripts. Analysis of RNA-seq data also revealed that PABPN1 controls the expression of many human genes via intron retention. Notably, PABPN1-dependent intron retention events mostly affected 3'-terminal introns and were insensitive to PAXT and NEXT deficiencies. Our findings thus disclose a role for PABPN1 in restricting nuclear export of intron-retained transcripts and reinforce the interdependence between terminal intron splicing, 3' end processing, and polyadenylation.<br /> (© 2023 Kwiatek et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Details

Language :
English
ISSN :
1469-9001
Volume :
29
Issue :
5
Database :
MEDLINE
Journal :
RNA (New York, N.Y.)
Publication Type :
Academic Journal
Accession number :
36754576
Full Text :
https://doi.org/10.1261/rna.079294.122