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PXD065356-1

PXD065356 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleLENG8 mediates nuclear retention and degradation of misprocessed mRNAs and noncoding RNAs
DescriptionIncompletely 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.
HostingRepositoryPRIDE
AnnounceDate2026-03-30
AnnouncementXMLSubmission_2026-03-29_16:35:17.236.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterClinton Yu
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-06-23 16:36:01ID requested
12026-03-29 16:35:18announced
Publication List
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;
Keyword List
submitter keyword: Misprocessed RNAs, RNA nuclear retention, RNA degradation, LENG8
Contact List
Yongsheng Shi
contact affiliationDepartment of Microbiology & Molecular Genetics University of California, Irvine Irvine, California, 92697 USA
contact emailyongshes@uci.edu
lab head
Clinton Yu
contact affiliationUniversity of California, Irvine
contact emailclinton.yu@uci.edu
dataset submitter
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Dataset FTP location
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