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RNA. 2014 Jan;20(1):88-102. doi: 10.1261/rna.042531.113. Epub 2013 Nov 19.

The C-terminal extension of Lsm4 interacts directly with the 3' end of the histone mRNP and is required for efficient histone mRNA degradation.

Abstract

Metazoan replication-dependent histone mRNAs are the only known eukaryotic mRNAs that lack a poly(A) tail, ending instead in a conserved stem-loop sequence, which is bound to the stem-loop binding protein (SLBP) on the histone mRNP. Histone mRNAs are rapidly degraded when DNA synthesis is inhibited in S phase in mammalian cells. Rapid degradation of histone mRNAs is initiated by oligouridylation of the 3' end of histone mRNAs and requires the cytoplasmic Lsm1-7 complex, which can bind to the oligo(U) tail. An exonuclease, 3'hExo, forms a ternary complex with SLBP and the stem-loop and is required for the initiation of histone mRNA degradation. The Lsm1-7 complex is also involved in degradation of polyadenylated mRNAs. It binds to the oligo(A) tail remaining after deadenylation, inhibiting translation and recruiting the enzymes required for decapping. Whether the Lsm1-7 complex interacts directly with other components of the mRNP is not known. We report here that the C-terminal extension of Lsm4 interacts directly with the histone mRNP, contacting both SLBP and 3'hExo. Mutants in the C-terminal tail of Lsm4 that prevent SLBP and 3'hExo binding reduce the rate of histone mRNA degradation when DNA synthesis is inhibited.

KEYWORDS:

ERI1; Lsm proteins; SLBP; histone mRNA; mRNA degradation

PMID:
24255165
PMCID:
PMC3866647
DOI:
10.1261/rna.042531.113
[Indexed for MEDLINE]
Free PMC Article

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