A Glycine-rich Domain of HnRNP H/F Promotes Nucleocytoplasmic Shuttling and Nuclear Import Through an Interaction with Transportin 1

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2010 Mar 24

PMID 20308327

Citations 34

Authors

Courtney M Van Dusen

Lily Yee

Lisa M McNally

Mark T McNally

Affiliations

Soon will be listed here.

Abstract

Heterogeneous nuclear ribonucleoprotein (hnRNP) H and F are members of a closely related subfamily of hnRNP proteins that are implicated in many aspects of RNA processing. hnRNP H and F are alternative splicing factors for numerous U2- and U12-dependent introns. The proteins have three RNA binding domains and two glycine-rich domains and localize to both the nucleus and cytoplasm, but little is known about which domains govern subcellular localization or splicing activity. We show here that the central glycine-tyrosine-arginine-rich (GYR) domain is responsible for nuclear localization, and a nonclassical nuclear localization signal (NLS) was mapped to a short, highly conserved sequence whose activity was compromised by point mutations. Glutathione S-transferase (GST) pulldown assays demonstrated that the hnRNP H NLS interacts with the import receptor transportin 1. Finally, we show that hnRNP H/F are transcription-dependent shuttling proteins. Collectively, the results suggest that hnRNP H and F are GYR domain-dependent shuttling proteins whose posttranslational modifications may alter nuclear localization and hence function.

Citing Articles

hnRNP H controls alternative splicing of human papillomavirus type 16 E1, E6, E7, and E6^E7 mRNAs via GGG motifs.

Jonsson J, Zhai Q, Schwartz S, Kajitani N J Virol. 2024; 98(10):e0095124.

PMID: 39287390 PMC: 11494879. DOI: 10.1128/jvi.00951-24.

The hnRNP A2B1 is important for the replication of SFTSV and other RNA viruses.

Zhang X, Yan L, Liu B, Zhou C, Yu X Microbiol Spectr. 2024; 12(10):e0082924.

PMID: 39166862 PMC: 11448443. DOI: 10.1128/spectrum.00829-24.

hnRNPH1 maintains mitochondrial homeostasis by establishing NRF1/DRP1 retrograde signaling under mitochondrial stress.

Zhao L, Zou X, Deng J, Sun B, Li Y, Zhao L Cell Death Differ. 2024; 32(1):118-133.

PMID: 38898233 PMC: 11742414. DOI: 10.1038/s41418-024-01331-4.

circGlis3 promotes β-cell dysfunction by binding to heterogeneous nuclear ribonucleoprotein F and encoding Glis3-348aa protein.

Xiong L, Gong Y, Liu H, Huang L, Zeng Z, Zheng X iScience. 2024; 27(1):108680.

PMID: 38226164 PMC: 10788204. DOI: 10.1016/j.isci.2023.108680.

Research Progress on the Structural and Functional Roles of hnRNPs in Muscle Development.

Li Z, Wei H, Hu D, Li X, Guo Y, Ding X Biomolecules. 2023; 13(10).

PMID: 37892116 PMC: 10604023. DOI: 10.3390/biom13101434.

References

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

McNally L, Yee L, McNally M . Heterogeneous nuclear ribonucleoprotein H is required for optimal U11 small nuclear ribonucleoprotein binding to a retroviral RNA-processing control element: implications for U12-dependent RNA splicing. J Biol Chem. 2005; 281(5):2478-88. DOI: 10.1074/jbc.M511215200. View

Matunis M, Xing J, Dreyfuss G . The hnRNP F protein: unique primary structure, nucleic acid-binding properties, and subcellular localization. Nucleic Acids Res. 1994; 22(6):1059-67. PMC: 307930. DOI: 10.1093/nar/22.6.1059. View

Nasim F, Hutchison S, Cordeau M, Chabot B . High-affinity hnRNP A1 binding sites and duplex-forming inverted repeats have similar effects on 5' splice site selection in support of a common looping out and repression mechanism. RNA. 2002; 8(8):1078-89. PMC: 1370318. DOI: 10.1017/s1355838202024056. View

Fischer U, Huber J, Boelens W, Mattaj I, Luhrmann R . The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell. 1995; 82(3):475-83. DOI: 10.1016/0092-8674(95)90436-0. View

Pan Q, Shai O, Misquitta C, Zhang W, Saltzman A, Mohammad N . Revealing global regulatory features of mammalian alternative splicing using a quantitative microarray platform. Mol Cell. 2004; 16(6):929-41. DOI: 10.1016/j.molcel.2004.12.004. View

Johnson J, Castle J, Garrett-Engele P, Kan Z, Loerch P, Armour C . Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science. 2003; 302(5653):2141-4. DOI: 10.1126/science.1090100. View

Carpenter B, Mackay C, Alnabulsi A, MacKay M, Telfer C, Melvin W . The roles of heterogeneous nuclear ribonucleoproteins in tumour development and progression. Biochim Biophys Acta. 2005; 1765(2):85-100. DOI: 10.1016/j.bbcan.2005.10.002. View

Allemand E, Guil S, Myers M, Moscat J, Caceres J, Krainer A . Regulation of heterogenous nuclear ribonucleoprotein A1 transport by phosphorylation in cells stressed by osmotic shock. Proc Natl Acad Sci U S A. 2005; 102(10):3605-10. PMC: 553333. DOI: 10.1073/pnas.0409889102. View

10.

Blanchette M, Chabot B . Modulation of exon skipping by high-affinity hnRNP A1-binding sites and by intron elements that repress splice site utilization. EMBO J. 1999; 18(7):1939-52. PMC: 1171279. DOI: 10.1093/emboj/18.7.1939. View

11.

Kalifa Y, Huang T, Rosen L, Chatterjee S, Gavis E . Glorund, a Drosophila hnRNP F/H homolog, is an ovarian repressor of nanos translation. Dev Cell. 2006; 10(3):291-301. DOI: 10.1016/j.devcel.2006.01.001. View

12.

Dominguez C, Allain F . NMR structure of the three quasi RNA recognition motifs (qRRMs) of human hnRNP F and interaction studies with Bcl-x G-tract RNA: a novel mode of RNA recognition. Nucleic Acids Res. 2006; 34(13):3634-45. PMC: 1540728. DOI: 10.1093/nar/gkl488. View

13.

van Der Houven Van Oordt W, Diaz-Meco M, Lozano J, Krainer A, Moscat J, Caceres J . The MKK(3/6)-p38-signaling cascade alters the subcellular distribution of hnRNP A1 and modulates alternative splicing regulation. J Cell Biol. 2000; 149(2):307-16. PMC: 2175157. DOI: 10.1083/jcb.149.2.307. View

14.

Coles J, Hallegger M, Smith C . A nonsense exon in the Tpm1 gene is silenced by hnRNP H and F. RNA. 2008; 15(1):33-43. PMC: 2612778. DOI: 10.1261/rna.1225209. View

15.

Chen C, Kobayashi R, Helfman D . Binding of hnRNP H to an exonic splicing silencer is involved in the regulation of alternative splicing of the rat beta-tropomyosin gene. Genes Dev. 1999; 13(5):593-606. PMC: 316507. DOI: 10.1101/gad.13.5.593. View

16.

McNally L, McNally M . U1 small nuclear ribonucleoprotein and splicing inhibition by the rous sarcoma virus negative regulator of splicing element. J Virol. 1999; 73(3):2385-93. PMC: 104484. DOI: 10.1128/JVI.73.3.2385-2393.1999. View

17.

Chou M, Rooke N, Turck C, Black D . hnRNP H is a component of a splicing enhancer complex that activates a c-src alternative exon in neuronal cells. Mol Cell Biol. 1998; 19(1):69-77. PMC: 83866. DOI: 10.1128/MCB.19.1.69. View

18.

Guo D, Han J, Adam B, Colburn N, Wang M, Dong Z . Proteomic analysis of SUMO4 substrates in HEK293 cells under serum starvation-induced stress. Biochem Biophys Res Commun. 2005; 337(4):1308-18. DOI: 10.1016/j.bbrc.2005.09.191. View

19.

Liu Q, Dreyfuss G . In vivo and in vitro arginine methylation of RNA-binding proteins. Mol Cell Biol. 1995; 15(5):2800-8. PMC: 230511. DOI: 10.1128/MCB.15.5.2800. View

20.

Pinol-Roma S, Dreyfuss G . Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm. Nature. 1992; 355(6362):730-2. DOI: 10.1038/355730a0. View