PXD065356

PXD065356 is an original dataset announced via ProteomeXchange.

Title	LENG8 mediates nuclear retention and degradation of misprocessed mRNAs and noncoding RNAs
Description	Incompletely processed and misprocessed mRNAs as well as numerous noncoding RNAs are retained in the nucleus and often degraded, and defects in this quality control mechanism have been linked to various diseases, including cancer and neurodegeneration. However, the underlying mechanisms remain poorly understood. Here we show that LENG8 is recruited to pre-mRNAs by splicing factors, including the U1 snRNP. Once RNA-bound, LENG8 is both necessary and sufficient to sequester RNA in the nucleus. LENG8 depletion leads to the leakage of misprocessed mRNAs, including intronically polyadenylated and intron-retained mRNAs, as well as noncoding RNAs into the cytoplasm. Mechanistically, we showed that LENG8 binds to PCID2 and SEM1 to form an evolutionarily conserved complex, referred to as REX (repressor of export), and causes RNA nuclear retention by acting as a dominant negative factor for the essential mRNA export factor TREX2. Finally, LENG8 promotes RNA degradation by recruiting the ZFC3H1-MTR4-exosome complex. Thus, LENG8 is a key quality control factor that keeps pre-mRNAs in the nucleus until they are fully and correctly processed.
HostingRepository	PRIDE
AnnounceDate	2026-03-30
AnnouncementXML	Submission_2026-03-29_16:35:17.236.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Clinton Yu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-23 16:36:01	ID requested
⏵ 1	2026-03-29 16:35:18	announced

Tian L, Liu L, Yoon Y, Soles LV, Valdez M, Jeong J, Yu C, Huang L, Shi Y, LENG8 mediates RNA nuclear retention and degradation in eukaryotes. Mol Cell, ():(2026) [pubmed]

10.1016/j.molcel.2026.02.023;

submitter keyword: Misprocessed RNAs, RNA nuclear retention, RNA degradation, LENG8

Yongsheng Shi
contact affiliation	Department of Microbiology & Molecular Genetics University of California, Irvine Irvine, California, 92697 USA
contact email	yongshes@uci.edu
lab head
Clinton Yu
contact affiliation	University of California, Irvine
contact email	clinton.yu@uci.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/03/PXD065356

PRIDE project URI

• PRIDE
  1. PXD065356
     1. Label: PRIDE project
     2. Name: LENG8 mediates nuclear retention and degradation of misprocessed mRNAs and noncoding RNAs