Uncoupling of nucleo-cytoplasmic RNA export and localization during stress.
Active Transport, Cell Nucleus
/ genetics
Adenosine
/ chemistry
Cell Nucleus
/ genetics
Cytoplasm
Cytoplasmic Granules
/ genetics
Cytoplasmic Structures
/ genetics
Exons
/ genetics
Humans
Nuclear Pore Complex Proteins
/ genetics
RNA
/ genetics
RNA Splicing
/ genetics
RNA Transport
/ genetics
RNA, Long Noncoding
/ genetics
RNA, Messenger
/ genetics
RNA-Binding Proteins
/ genetics
Stress, Physiological
/ genetics
Tubercidin
/ chemistry
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
21 05 2019
21 05 2019
Historique:
accepted:
02
03
2019
revised:
26
02
2019
received:
31
10
2018
pubmed:
14
3
2019
medline:
26
11
2019
entrez:
14
3
2019
Statut:
ppublish
Résumé
Eukaryotic cells contain sub-cellular compartments that are not membrane bound. Some structures are always present, such as nuclear speckles that contain RNA-binding proteins (RBPs) and poly(A)+ RNAs. Others, like cytoplasmic stress granules (SGs) that harbor mRNAs and RBPs, are induced upon stress. When we examined the formation and composition of nuclear speckles during stress induction with tubercidin, an adenosine analogue previously shown to affect nuclear speckle composition, we unexpectedly found that it also led to the formation of SGs and to the inhibition of several crucial steps of RNA metabolism in cells, thereby serving as a potent inhibitor of the gene expression pathway. Although transcription and splicing persisted under this stress, RBPs and mRNAs were mislocalized in the nucleus and cytoplasm. Specifically, lncRNA and RBP localization to nuclear speckles was disrupted, exon junction complex (EJC) recruitment to mRNA was reduced, mRNA export was obstructed, and cytoplasmic poly(A)+ RNAs localized in SGs. Furthermore, nuclear proteins that participate in mRNA export, such as nucleoporins and mRNA export adaptors, were mislocalized to SGs. This study reveals structural aspects of granule assembly in cells, and describes how the flow of RNA from the nucleus to the cytoplasm is severed under stress.
Identifiants
pubmed: 30864659
pii: 5377475
doi: 10.1093/nar/gkz168
pmc: PMC6511838
doi:
Substances chimiques
Nuclear Pore Complex Proteins
0
RNA, Long Noncoding
0
RNA, Messenger
0
RNA-Binding Proteins
0
RNA
63231-63-0
Adenosine
K72T3FS567
Tubercidin
M351LCX45Y
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4778-4797Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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