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PMID: 6577433 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Use of a cDNA clone for the fourth component of human complement (C4) for analysis of a genetic deficiency of C4 in guinea pig.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 80 ·No. 17 ·1983-09-00 ·Pages 5387-91

Whitehead AS, Goldberger G, Woods DE, Markham AF, Colten HR

Abstract

A cDNA clone for the fourth complement component (C4), pC4AL1, has been isolated from a human adult liver cDNA library by using a synthetic oligonucleotide mixture containing all 384 possible sequences coding for residues 14-21 of the C4 gamma-chain amino acid sequence. This clone spans the entire C4 gamma-chain coding sequence and includes a short 3' untranslated region, a poly(A) recognition site, and 16 nucleotides of the poly(A) tail. The 5' end of the clone begins 18 nucleotides upstream from the amino terminus of the C4 gamma chain and codes for Arg-Asn-Arg-Arg-Arg-Arg, a highly charged proteolytic cleavage site involved in the processing of pro-C4 to native C4. Liver mRNA preparations from C4-deficient guinea pigs were incapable of directing synthesis of pro-C4 or C4 peptides in cell-free translation experiments. Southern blot analysis using pC4AL1 as a hybridization probe of C4-deficient guinea pig DNA established that the deficiency is not the result of deletion of the entire C4 gene. RNA blot analysis using pC4AL1 as a hybridization probe of normal guinea pig liver mRNA revealed a C4 mRNA of 5.0 kilobases (kb). No such mRNA species was observed in C4-deficient guinea pig liver mRNA; however, a 7.0-kb RNA was detected, indicating the presence of a C4 precursor RNA. These results suggest that the basis of C4 deficiency in the guinea pig is a post-transcriptional defect in the processing of C4 precursor RNA to mature C4 mRNA.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Cloning, Molecular Complement C4/deficiency,genetics DNA/metabolism Guinea Pigs Humans Liver/metabolism Major Histocompatibility Complex Molecular Weight Nucleic Acid Hybridization Plasmids Protein Biosynthesis RNA, Messenger/genetics
Chemicals
Complement C4 RNA, Messenger DNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Whitehead A S
Goldberger G
Woods D E
Markham A F
Colten H R
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37 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.80.17.5387
Published
1983-09-00
Pages
5387-91
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC384261
Subset
IM
Grants
NIAID NIH HHS · AI15033 · United States
NIAID NIH HHS · AI18612 · United States
NICHD NIH HHS · HD17461 · United States
Databases
GENBANK
K00830
External Links
PubMed source DOI: 10.1073/pnas.80.17.5387 PMC Full Text View journal details
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