Nuclear import of cytoplasmic poly(A) binding protein restricts gene expression via hyperadenylation and nuclear retention of mRNA

TitleNuclear import of cytoplasmic poly(A) binding protein restricts gene expression via hyperadenylation and nuclear retention of mRNA
Publication TypeJournal Article
Year of Publication2010
AuthorsKumar RG, Glaunsinger BA
JournalMolecular and cellular biology
Volume30
Issue21
Pagination4996-5008
Date Published2010 Nov
ISSN1098-5549
KeywordsActive Transport, Cell Nucleus, Animals, Base Sequence, Cell Line, Cercopithecus aethiops, COS Cells, Cytoplasm, Gene Expression Regulation, Gene Knockdown Techniques, HeLa Cells, Herpesvirus 8, Human, Humans, Poly(A)-Binding Protein I, Polynucleotide Adenylyltransferase, Recombinant Proteins, RNA Processing, Post-Transcriptional, RNA, Messenger, RNA, Small Interfering, Viral Proteins
AbstractPoly(A) tail length is emerging as an important marker of mRNA fate, where deviations from the canonical length can signal degradation or nuclear retention of transcripts. Pathways regulating polyadenylation thus have the potential to broadly influence gene expression. Here we demonstrate that accumulation of cytoplasmic poly(A) binding protein (PABPC) in the nucleus, which can occur during viral infection or other forms of cellular stress, causes mRNA hyperadenylation and nuclear accumulation of poly(A) RNA. This inhibits gene expression but does not affect mRNA stability. Unexpectedly, PABPC-induced hyperadenylation can occur independently of mRNA 3'-end processing yet requires the canonical mRNA poly(A) polymerase II. We find that nuclear PABPC-induced hyperadenylation is triggered by multiple divergent viral factors, suggesting that altering the subcellular localization of PABPC may be a commonly used mechanism to regulate cellular gene expression in a polyadenylation-linked manner.
DOI10.1128/MCB.00600-10
Alternate JournalMol. Cell. Biol.