Heterogeneous Nuclear Ribonucleoproteins (hnRNPs) in Cellular Processes: Focus on HnRNP E1's Multifunctional Regulatory Roles

Overview

Journal RNA

Specialty Molecular Biology

Date 2010 Jun 30

PMID 20584894

Citations 164

Authors

Arindam Chaudhury

Praveen Chander

Philip H Howe

Affiliations

Soon will be listed here.

Abstract

Heterogeneous nuclear ribonucleoproteins (hnRNPs) comprise a family of RNA-binding proteins. The complexity and diversity associated with the hnRNPs render them multifunctional, involved not only in processing heterogeneous nuclear RNAs (hnRNAs) into mature mRNAs, but also acting as trans-factors in regulating gene expression. Heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1), a subgroup of hnRNPs, is a KH-triple repeat containing RNA-binding protein. It is encoded by an intronless gene arising from hnRNP E2 through a retrotransposition event. hnRNP E1 is ubiquitously expressed and functions in regulating major steps of gene expression, including pre-mRNA processing, mRNA stability, and translation. Given its wide-ranging functions in the nucleus and cytoplasm and interaction with multiple proteins, we propose a post-transcriptional regulon model that explains hnRNP E1's widespread functional diversity.

Citing Articles

Downregulation of hnRNPA1 inhibits hepatocellular carcinoma cell progression by modulating alternative splicing of ZNF207 exon 9.

Ouyang Q, He W, Guo Y, Li L, Mao Y, Li X Front Oncol. 2025; 14():1517459.

PMID: 39834948 PMC: 11743940. DOI: 10.3389/fonc.2024.1517459.

Heterogeneous Ribonucleoprotein K Is a Host Regulatory Factor of Chikungunya Virus Replication in Astrocytes.

Pieterse L, McDonald M, Abraham R, Griffin D Viruses. 2025; 16(12.

PMID: 39772225 PMC: 11680317. DOI: 10.3390/v16121918.

Combining Quantitative Proteomics and Interactomics for a Deeper Insight into Molecular Differences between Human Cell Lines.

Bakhtina A, Wippel H, Chavez J, Bruce J J Proteome Res. 2024; 23(12):5360-5371.

PMID: 39453897 PMC: 11867029. DOI: 10.1021/acs.jproteome.4c00503.

Regulation of HNRNP family by post-translational modifications in cancer.

Li B, Wen M, Gao F, Wang Y, Wei G, Duan Y Cell Death Discov. 2024; 10(1):427.

PMID: 39366930 PMC: 11452504. DOI: 10.1038/s41420-024-02198-7.

The up-regulation of SYNCRIP promotes the proliferation and tumorigenesis via DNMT3A/p16 in colorectal cancer.

Li C, Lu T, Chen H, Yu Z, Chen C Sci Rep. 2024; 14(1):21570.

PMID: 39284825 PMC: 11405714. DOI: 10.1038/s41598-024-59575-6.

References

Shamoo Y, Krueger U, Rice L, Williams K, Steitz T . Crystal structure of the two RNA binding domains of human hnRNP A1 at 1.75 A resolution. Nat Struct Biol. 1997; 4(3):215-22. DOI: 10.1038/nsb0397-215. View

Anderson P . Post-transcriptional regulons coordinate the initiation and resolution of inflammation. Nat Rev Immunol. 2009; 10(1):24-35. DOI: 10.1038/nri2685. View

Siomi H, Dreyfuss G . A nuclear localization domain in the hnRNP A1 protein. J Cell Biol. 1995; 129(3):551-60. PMC: 2120450. DOI: 10.1083/jcb.129.3.551. View

Beyer A, Christensen M, Walker B, Lestourgeon W . Identification and characterization of the packaging proteins of core 40S hnRNP particles. Cell. 1977; 11(1):127-38. DOI: 10.1016/0092-8674(77)90323-3. View

Cao J, Cui Y, Long Z, Dai Z, Lin J, Liang Y . Pluripotency-associated genes in human nasopharyngeal carcinoma CNE-2 cells are reactivated by a unique epigenetic sub-microenvironment. BMC Cancer. 2010; 10:68. PMC: 2837014. DOI: 10.1186/1471-2407-10-68. View

Caceres J, Stamm S, Helfman D, Krainer A . Regulation of alternative splicing in vivo by overexpression of antagonistic splicing factors. Science. 1994; 265(5179):1706-9. DOI: 10.1126/science.8085156. View

Samarina O, Lukanidin E, Molnar J, Georgiev G . Structural organization of nuclear complexes containing DNA-like RNA. J Mol Biol. 1968; 33(1):251-63. DOI: 10.1016/0022-2836(68)90292-1. View

Guil S, Gattoni R, Carrascal M, Abian J, Stevenin J, Bach-Elias M . Roles of hnRNP A1, SR proteins, and p68 helicase in c-H-ras alternative splicing regulation. Mol Cell Biol. 2003; 23(8):2927-41. PMC: 152554. DOI: 10.1128/MCB.23.8.2927-2941.2003. View

Thyagarajan A, Szaro B . Phylogenetically conserved binding of specific K homology domain proteins to the 3'-untranslated region of the vertebrate middle neurofilament mRNA. J Biol Chem. 2004; 279(48):49680-8. DOI: 10.1074/jbc.M408915200. View

10.

Borissova O, KRICHEVSKAYA A, Samarina O . Structural investigation of nuclear RNP particles containing pre-mRNA by different fluorescence techniques. Nucleic Acids Res. 1981; 9(3):663-81. PMC: 327229. DOI: 10.1093/nar/9.3.663. View

11.

Baharvand H, Fathi A, Gourabi H, Mollamohammadi S, Hosseini Salekdeh G . Identification of mouse embryonic stem cell-associated proteins. J Proteome Res. 2007; 7(1):412-23. DOI: 10.1021/pr700560t. View

12.

Ostareck D, Ostareck-Lederer A, Wilm M, Thiele B, Mann M, Hentze M . mRNA silencing in erythroid differentiation: hnRNP K and hnRNP E1 regulate 15-lipoxygenase translation from the 3' end. Cell. 1997; 89(4):597-606. DOI: 10.1016/s0092-8674(00)80241-x. View

13.

Grishin N . KH domain: one motif, two folds. Nucleic Acids Res. 2001; 29(3):638-43. PMC: 30387. DOI: 10.1093/nar/29.3.638. View

14.

Pinol-Roma S, Choi Y, Matunis M, Dreyfuss G . Immunopurification of heterogeneous nuclear ribonucleoprotein particles reveals an assortment of RNA-binding proteins. Genes Dev. 1988; 2(2):215-27. DOI: 10.1101/gad.2.2.215. View

15.

Bomsztyk K, Van Seuningen I, Suzuki H, Denisenko O, Ostrowski J . Diverse molecular interactions of the hnRNP K protein. FEBS Lett. 1997; 403(2):113-5. DOI: 10.1016/s0014-5793(97)00041-0. View

16.

Conaway R, Conaway J . ATP activates transcription initiation from promoters by RNA polymerase II in a reversible step prior to RNA synthesis. J Biol Chem. 1988; 263(6):2962-8. View

17.

Regnier P, GRUNBERG-MANAGO M, Portier C . Nucleotide sequence of the pnp gene of Escherichia coli encoding polynucleotide phosphorylase. Homology of the primary structure of the protein with the RNA-binding domain of ribosomal protein S1. J Biol Chem. 1987; 262(1):63-8. View

18.

Pickering B, Mitchell S, Evans J, Willis A . Polypyrimidine tract binding protein and poly r(C) binding protein 1 interact with the BAG-1 IRES and stimulate its activity in vitro and in vivo. Nucleic Acids Res. 2003; 31(2):639-46. PMC: 140511. DOI: 10.1093/nar/gkg146. View

19.

Kiledjian M, Wang X, Liebhaber S . Identification of two KH domain proteins in the alpha-globin mRNP stability complex. EMBO J. 1995; 14(17):4357-64. PMC: 394520. DOI: 10.1002/j.1460-2075.1995.tb00110.x. View

20.

Bomsztyk K, Denisenko O, Ostrowski J . hnRNP K: one protein multiple processes. Bioessays. 2004; 26(6):629-38. DOI: 10.1002/bies.20048. View