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PMID: 7556077 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Identification of two KH domain proteins in the alpha-globin mRNP stability complex.

The EMBO journal ·Vol. 14 ·No. 17 ·1995-09-01 ·Pages 4357-64

Kiledjian M, Wang X, Liebhaber SA

Abstract

Accumulation of globin mRNAs during erythroid differentiation is dependent on their extraordinary stability. The longevity of human alpha-globin mRNA is associated with a ribonucleoprotein complex (alpha-complex) formed on the 3' untranslated region (3'UTR). One or more of the proteins within this alpha-complex contain strong polycytosine [poly(C)] binding (alpha PCB) activity. In the present report we purify alpha PCB activity from human erythroid K562 cells. Although not able to bind the alpha-globin 3'UTR directly, alpha PCB activity is sufficient to complement alpha-complex formation in a cytosolic extract depleted of poly(C) binding activity. Peptide microsequencing demonstrates that alpha PCB activity contains two structurally related poly(C) binding proteins. These two proteins, alpha-complex protein (alpha CP)-1 and -2, have an overall structural identity of 80% and contain three repeats of the K homology (KH) domain which is found in a subset of RNA binding proteins. Epitope-tagged recombinant alpha CP-1 and alpha CP-2 expressed in cells are each incorporated into the alpha-complex. We conclude that alpha CP-1 and alpha CP-2, members of the KH domain RNA binding protein family, are involved in formation of a sequence-specific alpha-globin mRNP complex associated with alpha-globin mRNA stability. As such this represents the first example of a specific function for this class of proteins and suggests potential roles for other members of this protein family.

MeSH Terms
Amino Acid Sequence Base Sequence Binding Sites Cell Line Globins/biosynthesis Heterogeneous-Nuclear Ribonucleoproteins Humans Leukemia, Erythroblastic, Acute Molecular Sequence Data Open Reading Frames Poly C/metabolism RNA, Messenger/metabolism Ribonucleoproteins/chemistry,isolation & purification,metabolism Sequence Homology, Amino Acid Tumor Cells, Cultured
Chemicals
Heterogeneous-Nuclear Ribonucleoproteins RNA, Messenger Ribonucleoproteins messenger ribonucleoprotein Poly C Globins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kiledjian M
Howard Hughes Medical Institute, Department of Genetics, Philadelphia 19104-6145, USA.
Wang X
Liebhaber S A
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1995-09-01
Pages
4357-64
Language
English
Region
England
NLM ID
8208664
PMCID
PMC394520
Subset
IM
Grants
NHLBI NIH HHS · P60-HL38632 · United States
Databases
GENBANK
U24223
External Links
PubMed source PMC Full Text View journal details
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