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PMID: 10913178 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A U-rich element in the 5' untranslated region is necessary for the translation of p27 mRNA.

Molecular and cellular biology ·Vol. 20 ·No. 16 ·2000-08-00 ·Pages 5947-59

Millard SS, Vidal A, Markus M, Koff A

Abstract

Increased translation of p27 mRNA correlates with withdrawal of cells from the cell cycle. This raised the possibility that antimitogenic signals might mediate their effects on p27 expression by altering complexes that formed on p27 mRNA, regulating its translation. In this report, we identify a U-rich sequence in the 5' untranslated region (5'UTR) of p27 mRNA that is necessary for efficient translation in proliferating and nonproliferating cells. We show that a number of factors bind to the 5'UTR in vitro in a manner dependent on the U-rich element, and their availability in the cytosol is controlled in a growth- and cell cycle-dependent fashion. One of these factors is HuR, a protein previously implicated in mRNA stability, transport, and translation. Another is hnRNP C1 and C2, proteins implicated in mRNA processing and the translation of a specific subset of mRNAs expressed in differentiated cells. In lovastatin-treated MDA468 cells, the mobility of the associated hnRNP C1 and C2 proteins changed, and this correlated with increased p27 expression. Together, these data suggest that the U-rich dependent RNP complex on the 5'UTR may regulate the translation of p27 mRNA and may be a target of antimitogenic signals.

MeSH Terms
5' Untranslated Regions/genetics Base Sequence Cell Cycle/genetics HeLa Cells Humans Microfilament Proteins/genetics Molecular Sequence Data Muscle Proteins Protein Biosynthesis RNA, Messenger/genetics
Chemicals
5' Untranslated Regions Microfilament Proteins Muscle Proteins RNA, Messenger Tagln protein, mouse
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Millard S S
Graduate Program in Cell Biology and Genetics, Weill Graduate School of Medical Sciences, Cornell University, New York, New York 10021, USA.
Vidal A
Markus M
Koff A
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.16.5947-5959.2000
Published
2000-08-00
Pages
5947-59
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC86072
Subset
IM
Grants
NCI NIH HHS · P30 CA008748 · United States
NIGMS NIH HHS · R01 GM052597 · United States
NCI NIH HHS · CA08748 · United States
NIGMS NIH HHS · GM52597 · United States
External Links
PubMed source DOI: 10.1128/MCB.20.16.5947-5959.2000 PMC Full Text View journal details
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