Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Dec;86(24):9788–9792. doi: 10.1073/pnas.86.24.9788

Primary structures of the heterogeneous nuclear ribonucleoprotein A2, B1, and C2 proteins: a diversity of RNA binding proteins is generated by small peptide inserts.

C G Burd 1, M S Swanson 1, M Görlach 1, G Dreyfuss 1
PMCID: PMC298587  PMID: 2557628

Abstract

We have isolated cDNAs for the major heterogeneous nuclear ribonucleoprotein (hnRNP) A2, B1, and C2 proteins and determined their nucleotide and deduced amino acid sequences. The A2 and B1 cDNAs are identical except for a 36-nucleotide in-frame insert in B1. Similarly, the sequence of the C2 protein cDNA is related to that of C1 in that C2 contains an extra 39 in-frame nucleotides. Therefore, the B1 amino acid sequence is identical to A2 except for the insertion of 12 amino acids near its amino terminus, and C1 and C2 are also identical to each other except for an extra 13 amino acids near the middle of C2. All three proteins are members of a large family of RNA binding proteins that contain the consensus sequence-type RNA binding domain (CS-RBD). The A2 and B1 proteins have a modular structure similar to that of the hnRNP protein A1: they contain two CS-RBDs and a glycine-rich auxiliary domain at the carboxyl terminus. The CS-RBDs of A2 and B1 have approximately 80% amino acid identity with those of A1, whereas the glycine-rich auxiliary domain is considerably more divergent with less than 30% of the amino acids being identical. These findings indicate that the addition of small peptides, probably by alternative pre-mRNA splicing, generates some of the diversity apparent among hnRNP proteins.

Full text

PDF
9788

Images in this article

9789Image
on p.9789
9789Image
on p.9789
9790Image
on p.9790
9790Image
on p.9790
9790Image
on p.9790
9790Image
on p.9790
9791Image
on p.9791

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adam S. A., Nakagawa T., Swanson M. S., Woodruff T. K., Dreyfuss G. mRNA polyadenylate-binding protein: gene isolation and sequencing and identification of a ribonucleoprotein consensus sequence. Mol Cell Biol. 1986 Aug;6(8):2932–2943. doi: 10.1128/mcb.6.8.2932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bandziulis R. J., Swanson M. S., Dreyfuss G. RNA-binding proteins as developmental regulators. Genes Dev. 1989 Apr;3(4):431–437. doi: 10.1101/gad.3.4.431. [DOI] [PubMed] [Google Scholar]
  3. Biamonti G., Buvoli M., Bassi M. T., Morandi C., Cobianchi F., Riva S. Isolation of an active gene encoding human hnRNP protein A1. Evidence for alternative splicing. J Mol Biol. 1989 Jun 5;207(3):491–503. doi: 10.1016/0022-2836(89)90459-2. [DOI] [PubMed] [Google Scholar]
  4. Bugler B., Bourbon H., Lapeyre B., Wallace M. O., Chang J. H., Amalric F., Olson M. O. RNA binding fragments from nucleolin contain the ribonucleoprotein consensus sequence. J Biol Chem. 1987 Aug 15;262(23):10922–10925. [PubMed] [Google Scholar]
  5. Buvoli M., Biamonti G., Tsoulfas P., Bassi M. T., Ghetti A., Riva S., Morandi C. cDNA cloning of human hnRNP protein A1 reveals the existence of multiple mRNA isoforms. Nucleic Acids Res. 1988 May 11;16(9):3751–3770. doi: 10.1093/nar/16.9.3751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Choi Y. D., Dreyfuss G. Monoclonal antibody characterization of the C proteins of heterogeneous nuclear ribonucleoprotein complexes in vertebrate cells. J Cell Biol. 1984 Dec;99(6):1997–1204. doi: 10.1083/jcb.99.6.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cobianchi F., SenGupta D. N., Zmudzka B. Z., Wilson S. H. Structure of rodent helix-destabilizing protein revealed by cDNA cloning. J Biol Chem. 1986 Mar 15;261(8):3536–3543. [PubMed] [Google Scholar]
  8. Dingwall C., Laskey R. A. Protein import into the cell nucleus. Annu Rev Cell Biol. 1986;2:367–390. doi: 10.1146/annurev.cb.02.110186.002055. [DOI] [PubMed] [Google Scholar]
  9. Dreyfuss G., Swanson M. S., Piñol-Roma S. Heterogeneous nuclear ribonucleoprotein particles and the pathway of mRNA formation. Trends Biochem Sci. 1988 Mar;13(3):86–91. doi: 10.1016/0968-0004(88)90046-1. [DOI] [PubMed] [Google Scholar]
  10. Haynes S. R., Rebbert M. L., Mozer B. A., Forquignon F., Dawid I. B. pen repeat sequences are GGN clusters and encode a glycine-rich domain in a Drosophila cDNA homologous to the rat helix destabilizing protein. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1819–1823. doi: 10.1073/pnas.84.7.1819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Herr W., Sturm R. A., Clerc R. G., Corcoran L. M., Baltimore D., Sharp P. A., Ingraham H. A., Rosenfeld M. G., Finney M., Ruvkun G. The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products. Genes Dev. 1988 Dec;2(12A):1513–1516. doi: 10.1101/gad.2.12a.1513. [DOI] [PubMed] [Google Scholar]
  12. Herrick G., Alberts B. Purification and physical characterization of nucleic acid helix-unwinding proteins from calf thymus. J Biol Chem. 1976 Apr 10;251(7):2124–2132. [PubMed] [Google Scholar]
  13. Kaufman R. J., Davies M. V., Pathak V. K., Hershey J. W. The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs. Mol Cell Biol. 1989 Mar;9(3):946–958. doi: 10.1128/mcb.9.3.946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kumar A., Williams K. R., Szer W. Purification and domain structure of core hnRNP proteins A1 and A2 and their relationship to single-stranded DNA-binding proteins. J Biol Chem. 1986 Aug 25;261(24):11266–11273. [PubMed] [Google Scholar]
  15. Lahiri D. K., Thomas J. O. A cDNA clone of the hnRNP C proteins and its homology with the single-stranded DNA binding protein UP2. Nucleic Acids Res. 1986 May 27;14(10):4077–4094. doi: 10.1093/nar/14.10.4077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Leser G. P., Escara-Wilke J., Martin T. E. Monoclonal antibodies to heterogeneous nuclear RNA-protein complexes. The core proteins comprise a conserved group of related polypeptides. J Biol Chem. 1984 Feb 10;259(3):1827–1833. [PubMed] [Google Scholar]
  17. Nakagawa T. Y., Swanson M. S., Wold B. J., Dreyfuss G. Molecular cloning of cDNA for the nuclear ribonucleoprotein particle C proteins: a conserved gene family. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2007–2011. doi: 10.1073/pnas.83.7.2007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Piñol-Roma S., Choi Y. D., Matunis M. J., Dreyfuss G. Immunopurification of heterogeneous nuclear ribonucleoprotein particles reveals an assortment of RNA-binding proteins. Genes Dev. 1988 Feb;2(2):215–227. doi: 10.1101/gad.2.2.215. [DOI] [PubMed] [Google Scholar]
  19. Preugschat F., Wold B. Isolation and characterization of a Xenopus laevis C protein cDNA: structure and expression of a heterogeneous nuclear ribonucleoprotein core protein. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9669–9673. doi: 10.1073/pnas.85.24.9669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Query C. C., Bentley R. C., Keene J. D. A common RNA recognition motif identified within a defined U1 RNA binding domain of the 70K U1 snRNP protein. Cell. 1989 Apr 7;57(1):89–101. doi: 10.1016/0092-8674(89)90175-x. [DOI] [PubMed] [Google Scholar]
  21. Riva S., Morandi C., Tsoulfas P., Pandolfo M., Biamonti G., Merrill B., Williams K. R., Multhaup G., Beyreuther K., Werr H. Mammalian single-stranded DNA binding protein UP I is derived from the hnRNP core protein A1. EMBO J. 1986 Sep;5(9):2267–2273. doi: 10.1002/j.1460-2075.1986.tb04494.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Struhl K. Helix-turn-helix, zinc-finger, and leucine-zipper motifs for eukaryotic transcriptional regulatory proteins. Trends Biochem Sci. 1989 Apr;14(4):137–140. doi: 10.1016/0968-0004(89)90145-X. [DOI] [PubMed] [Google Scholar]
  23. Swanson M. S., Dreyfuss G. Classification and purification of proteins of heterogeneous nuclear ribonucleoprotein particles by RNA-binding specificities. Mol Cell Biol. 1988 May;8(5):2237–2241. doi: 10.1128/mcb.8.5.2237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Swanson M. S., Nakagawa T. Y., LeVan K., Dreyfuss G. Primary structure of human nuclear ribonucleoprotein particle C proteins: conservation of sequence and domain structures in heterogeneous nuclear RNA, mRNA, and pre-rRNA-binding proteins. Mol Cell Biol. 1987 May;7(5):1731–1739. doi: 10.1128/mcb.7.5.1731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wilk H. E., Werr H., Friedrich D., Kiltz H. H., Schäfer K. P. The core proteins of 35S hnRNP complexes. Characterization of nine different species. Eur J Biochem. 1985 Jan 2;146(1):71–81. doi: 10.1111/j.1432-1033.1985.tb08621.x. [DOI] [PubMed] [Google Scholar]
  26. Williams K. R., Stone K. L., LoPresti M. B., Merrill B. M., Planck S. R. Amino acid sequence of the UP1 calf thymus helix-destabilizing protein and its homology to an analogous protein from mouse myeloma. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5666–5670. doi: 10.1073/pnas.82.17.5666. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES