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PMID: 11707415 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regulation of nuclear poly(A) addition controls the expression of immunoglobulin M secretory mRNA.

The EMBO journal ·Vol. 20 ·No. 22 ·2001-11-15 ·Pages 6443-52

Phillips C, Jung S, Gunderson SI

Abstract

B-cell differentiation is accompanied by a dramatic increase in cytoplasmic accumulation and stability of the IgM heavy chain (mu) secretory mRNA. Despite considerable effort, the mechanism is unknown. We have identified three short motifs upstream of the secretory poly(A) site, which, when mutated in the mu heavy chain gene, significantly increase the accumulation of the secretory form of poly(A)(+) mRNA relative to the membrane form and regulate the expression of the secretory poly(A) site in a developmental manner. We show that these motifs bind U1A and inhibit polyadenylation in vitro and in vivo. Overexpression of U1A in vivo results in the selective inhibition of the secretory form. Thus, this novel mechanism selectively controls post-cleavage expression of the mu secretory mRNA. We present evidence that this mechanism is used to regulate alternative expression of other genes.

MeSH Terms
Amino Acid Motifs Animals B-Lymphocytes/cytology Base Sequence Binding Sites Cattle Cell Differentiation Cell Nucleus/metabolism DNA Mutational Analysis Dose-Response Relationship, Drug Escherichia coli/metabolism Gene Expression Regulation HeLa Cells Humans Immunoglobulin M/biosynthesis,genetics Models, Genetic Molecular Sequence Data Mutation Plasmids/metabolism Poly A/metabolism Protein Binding RNA, Messenger/metabolism Recombinant Proteins/metabolism Ribonucleases/metabolism Transfection
Chemicals
Immunoglobulin M RNA, Messenger Recombinant Proteins Poly A Ribonucleases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Phillips C
Rutgers University, Nelson Labs Room A322, 604 Allison Road, Piscataway, NJ 08854, USA. catphill@rci.rutgers.edu
Jung S
Gunderson S I
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.22.6443
Email
catphill@rci.rutgers.edu
Published
2001-11-15
Pages
6443-52
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125739
Subset
IM
Grants
NIGMS NIH HHS · R01 GM057286 · United States
NIGMS NIH HHS · GM57286 · United States
External Links
PubMed source DOI: 10.1093/emboj/20.22.6443 PMC Full Text View journal details
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