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PMID: 15684398 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A CPSF-73 homologue is required for cell cycle progression but not cell growth and interacts with a protein having features of CPSF-100.

Molecular and cellular biology ·Vol. 25 ·No. 4 ·2005-02-00 ·Pages 1489-500

Dominski Z, Yang XC, Purdy M, Wagner EJ, Marzluff WF

Abstract

Formation of the mature 3' ends of the vast majority of cellular mRNAs occurs through cleavage and polyadenylation and requires a cleavage and polyadenylation specificity factor (CPSF) containing, among other proteins, CPSF-73 and CPSF-100. These two proteins belong to a superfamily of zinc-dependent beta-lactamase fold proteins with catalytic specificity for a wide range of substrates including nucleic acids. CPSF-73 contains a zinc-binding histidine motif involved in catalysis in other members of the beta-lactamase superfamily, whereas CPSF-100 has substitutions within the histidine motif and thus is unlikely to be catalytically active. Here we describe two previously unknown human proteins, designated RC-68 and RC-74, which are related to CPSF-73 and CPSF-100 and which form a complex in HeLa and mouse cells. RC-68 contains the intact histidine motif, and hence it might be a functional counterpart of CPSF-73, whereas RC-74 lacks this motif, thus resembling CPSF-100. In HeLa cells RC-68 is present in both the cytoplasm and the nucleus whereas RC-74 is exclusively nuclear. RC-74 does not interact with CPSF-73, and neither RC-68 nor RC-74 is found in a complex with CPSF-160, indicating that these two proteins form a separate entity independent of the CPSF complex and are likely involved in a pre-mRNA processing event other than cleavage and polyadenylation of the vast majority of cellular pre-mRNAs. RNA interference-mediated depletion of RC-68 arrests HeLa cells early in G(1) phase, but surprisingly the arrested cells continue growing and reach the size typical of G(2) cells. RC-68 is highly conserved from plants to humans and may function in conjunction with RC-74 in the 3' end processing of a distinct subset of cellular pre-mRNAs encoding proteins required for G(1) progression and entry into S phase.

MeSH Terms
Amino Acid Sequence Animals Cell Cycle/physiology Cell Enlargement Cell Nucleus/metabolism Cleavage And Polyadenylation Specificity Factor/metabolism Cytoplasm/metabolism HeLa Cells Histidine/metabolism Humans Mice Molecular Sequence Data Proteins/metabolism RNA, Small Interfering/metabolism Tumor Cells, Cultured Two-Hybrid System Techniques
Chemicals
Cleavage And Polyadenylation Specificity Factor Proteins RNA, Small Interfering Histidine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Dominski Zbigniew
Program in Molecular Biology and Biotechnology, CB #3280, University of North Carolina, Chapel Hill, NC 27599. dominski@med.unc.edu.
Yang Xiao-Cui
Purdy Matthew
Wagner Eric J
Marzluff William F
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.4.1489-1500.2005
Email
dominski@med.unc.edu
Published
2005-02-00
Pages
1489-500
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC548002
Subset
IM
Grants
NIGMS NIH HHS · R01 GM029832 · United States
NCI NIH HHS · T32 CA009156 · United States
NIGMS NIH HHS · GM29832 · United States
NCI NIH HHS · T32-CA09156 · United States
External Links
PubMed source DOI: 10.1128/MCB.25.4.1489-1500.2005 PMC Full Text View journal details
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