Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box - PubMed

Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box

M Kiledjian et al. EMBO J. 1992 Jul.

Abstract

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are thought to influence the structure of hnRNA and participate in the processing of hnRNA to mRNA. The hnRNP U protein is an abundant nucleoplasmic phosphoprotein that is the largest of the major hnRNP proteins (120 kDa by SDS-PAGE). HnRNP U binds pre-mRNA in vivo and binds both RNA and ssDNA in vitro. Here we describe the cloning and sequencing of a cDNA encoding the hnRNP U protein, the determination of its amino acid sequence and the delineation of a region in this protein that confers RNA binding. The predicted amino acid sequence of hnRNP U contains 806 amino acids (88,939 Daltons), and shows no extensive homology to any known proteins. The N-terminus is rich in acidic residues and the C-terminus is glycine-rich. In addition, a glutamine-rich stretch, a putative NTP binding site and a putative nuclear localization signal are present. It could not be defined from the sequence what segment of the protein confers its RNA binding activity. We identified an RNA binding activity within the C-terminal glycine-rich 112 amino acids. This region, designated U protein glycine-rich RNA binding region (U-gly), can by itself bind RNA. Furthermore, fusion of U-gly to a heterologous bacterial protein (maltose binding protein) converts this fusion protein into an RNA binding protein. A 26 amino acid peptide within U-gly is necessary for the RNA binding activity of the U protein. Interestingly, this peptide contains a cluster of RGG repeats with characteristic spacing and this motif is found also in several other RNA binding proteins. We have termed this region the RGG box and propose that it is an RNA binding motif and a predictor of RNA binding activity.

Similar articles

• hnRNP I, the polypyrimidine tract-binding protein: distinct nuclear localization and association with hnRNAs.

  Ghetti A, Piñol-Roma S, Michael WM, Morandi C, Dreyfuss G. Ghetti A, et al. Nucleic Acids Res. 1992 Jul 25;20(14):3671-8. doi: 10.1093/nar/20.14.3671. Nucleic Acids Res. 1992. PMID: 1641332 Free PMC article.

• The determinants of RNA-binding specificity of the heterogeneous nuclear ribonucleoprotein C proteins.

  Görlach M, Burd CG, Dreyfuss G. Görlach M, et al. J Biol Chem. 1994 Sep 16;269(37):23074-8. J Biol Chem. 1994. PMID: 8083209

• 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.

  Swanson MS, Nakagawa TY, LeVan K, Dreyfuss G. Swanson MS, et al. Mol Cell Biol. 1987 May;7(5):1731-9. doi: 10.1128/mcb.7.5.1731-1739.1987. Mol Cell Biol. 1987. PMID: 3110598 Free PMC article.

• Heterogeneous nuclear ribonucleoproteins (hnRNPs) in cellular processes: Focus on hnRNP E1's multifunctional regulatory roles.

  Chaudhury A, Chander P, Howe PH. Chaudhury A, et al. RNA. 2010 Aug;16(8):1449-62. doi: 10.1261/rna.2254110. Epub 2010 Jun 28. RNA. 2010. PMID: 20584894 Free PMC article. Review.

• The roles of heterogeneous nuclear ribonucleoproteins (hnRNP) in RNA metabolism.

  Weighardt F, Biamonti G, Riva S. Weighardt F, et al. Bioessays. 1996 Sep;18(9):747-56. doi: 10.1002/bies.950180910. Bioessays. 1996. PMID: 8831291 Review.

Cited by

• Vasa-Like DEAD-Box RNA Helicases of Schistosoma mansoni.

  Skinner DE, Rinaldi G, Suttiprapa S, Mann VH, Smircich P, Cogswell AA, Williams DL, Brindley PJ. Skinner DE, et al. PLoS Negl Trop Dis. 2012;6(6):e1686. doi: 10.1371/journal.pntd.0001686. Epub 2012 Jun 12. PLoS Negl Trop Dis. 2012. PMID: 22720105 Free PMC article.

• Cell division requires RNA eviction from condensing chromosomes.

  Sharp JA, Perea-Resa C, Wang W, Blower MD. Sharp JA, et al. J Cell Biol. 2020 Nov 2;219(11):e201910148. doi: 10.1083/jcb.201910148. J Cell Biol. 2020. PMID: 33053167 Free PMC article.

• An unbiased proteomics approach to identify human cytomegalovirus RNA-associated proteins.

  Lenarcic EM, Ziehr BJ, Moorman NJ. Lenarcic EM, et al. Virology. 2015 Jul;481:13-23. doi: 10.1016/j.virol.2015.02.008. Epub 2015 Mar 9. Virology. 2015. PMID: 25765003 Free PMC article.

• Nature-inspired engineering of an artificial ligase enzyme by domain fusion.

  Tong CL, Kanwar N, Morrone DJ, Seelig B. Tong CL, et al. Nucleic Acids Res. 2022 Oct 28;50(19):11175-11185. doi: 10.1093/nar/gkac858. Nucleic Acids Res. 2022. PMID: 36243966 Free PMC article.

• Crucial roles of different RNA-binding hnRNP proteins in Stem Cells.

  Xie W, Zhu H, Zhao M, Wang L, Li S, Zhao C, Zhou Y, Zhu B, Jiang X, Liu W, Ren C. Xie W, et al. Int J Biol Sci. 2021 Feb 8;17(3):807-817. doi: 10.7150/ijbs.55120. eCollection 2021. Int J Biol Sci. 2021. PMID: 33767590 Free PMC article. Review.

References

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Europe PubMed Central
  • Nature Publishing Group
  • PubMed Central
  • Wiley

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • BioCyc
  • Gene Ontology
  • GlyGen glycoinformatics resource