HNRNPR explained

Heterogeneous nuclear ribonucleoprotein R is a protein that in humans is encoded by the HNRNPR gene.^{[1] [2]}

Function

This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA-binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has three repeats of RRM domains that bind to RNAs and also contains a nuclear localization motif.^[2]

HNRNPR, together with its main RNA interacting partner, 7SK, is essential for axon growth in motoneurons.^[3] Depletion of HNRNPR from primary motoneurons inhibits axonal development, but it does not lead to enhanced loss of motor neurons.^[3] It also plays an important role in axonal β-actin mRNA translocation, binding directly to the 3'-UTR of β-actin mRNA.^[4]

HNRNPR enhances c-fos transcription in vitro by forming a complex with PC4 and Mediator cofactors.^[5]

Interactions

HNRNPR has been shown to interact with SMN1,^{[6] [7]} PRMT1,^{[8] [9]} TDP-43,^[10] and FUS/TLS.^[10]

Further reading

• Mourelatos Z, Abel L, Yong J, Kataoka N, Dreyfuss G . SMN interacts with a novel family of hnRNP and spliceosomal proteins . The EMBO Journal . 20 . 19 . 5443–52 . October 2001 . 11574476 . 125643 . 10.1093/emboj/20.19.5443 .
• Rossoll W, Kröning AK, Ohndorf UM, Steegborn C, Jablonka S, Sendtner M . Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: a role for Smn in RNA processing in motor axons? . Human Molecular Genetics . 11 . 1 . 93–105 . January 2002 . 11773003 . 10.1093/hmg/11.1.93 . free .
• Jurica MS, Licklider LJ, Gygi SR, Grigorieff N, Moore MJ . Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis . RNA . 8 . 4 . 426–39 . April 2002 . 11991638 . 1370266 . 10.1017/S1355838202021088 .
• Wada K, Inoue K, Hagiwara M . Identification of methylated proteins by protein arginine N-methyltransferase 1, PRMT1, with a new expression cloning strategy . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1591 . 1–3 . 1–10 . August 2002 . 12183049 . 10.1016/S0167-4889(02)00202-1 .
• Angenstein F, Evans AM, Settlage RE, Moran ST, Ling SC, Klintsova AY, Shabanowitz J, Hunt DF, Greenough WT . A receptor for activated C kinase is part of messenger ribonucleoprotein complexes associated with polyA-mRNAs in neurons . The Journal of Neuroscience . 22 . 20 . 8827–37 . October 2002 . 12388589 . 6757688 . 10.1523/jneurosci.22-20-08827.2002.
• Hassel S, Eichner A, Yakymovych M, Hellman U, Knaus P, Souchelnytskyi S . Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel electrophoresis and mass spectrometry . Proteomics . 4 . 5 . 1346–58 . May 2004 . 15188402 . 10.1002/pmic.200300770 . 6773754 .
• Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M . Nucleolar proteome dynamics . Nature . 433 . 7021 . 77–83 . January 2005 . 15635413 . 10.1038/nature03207 . 2005Natur.433...77A . 4344740 .
• Huang J, Chen XH, Wu K, Xu P . Cloning and expression of a novel isoform of heterogeneous nuclear ribonucleoprotein-R . NeuroReport . 16 . 7 . 727–30 . May 2005 . 15858414 . 10.1097/00001756-200505120-00014 . 42006801 .
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes . Genome Research . 16 . 1 . 55–65 . January 2006 . 16344560 . 1356129 . 10.1101/gr.4039406 .
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .
• Szafranski K, Schindler S, Taudien S, Hiller M, Huse K, Jahn N, Schreiber S, Backofen R, Platzer M . Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns . Genome Biology . 8 . 8 . R154 . 2007 . 17672918 . 2374985 . 10.1186/gb-2007-8-8-r154 . free .

Notes and References

1. Hassfeld W, Chan EK, Mathison DA, Portman D, Dreyfuss G, Steiner G, Tan EM . Molecular definition of heterogeneous nuclear ribonucleoprotein R (hnRNP R) using autoimmune antibody: immunological relationship with hnRNP P . Nucleic Acids Research . 26 . 2 . 439–45 . January 1998 . 9421497 . 147279 . 10.1093/nar/26.2.439 .
2. Web site: Entrez Gene: HNRPR heterogeneous nuclear ribonucleoprotein R.
3. Briese M, Saal-Bauernschubert L, Ji C, Moradi M, Ghanawi H, Uhl M, Appenzeller S, Backofen R, Sendtner M . hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons . Proceedings of the National Academy of Sciences of the United States of America . 115 . 12 . E2859-68 . March 2018 . 29507242 . 10.1073/pnas.1721670115 . 5866599 . 2018PNAS..115E2859B . 1091-6490 . free .
4. Glinka M, Herrmann T, Funk N, Havlicek S, Rossoll W, Winkler C, Sendtner M . The heterogeneous nuclear ribonucleoprotein-R is necessary for axonal beta-actin mRNA translocation in spinal motor neurons . Human Molecular Genetics . 19 . 10 . 1951–66 . 2010 . 20167579 . 10.1093/hmg/ddq073 . 1460-2083 . free .
5. Fukuda A, Nakadai T, Shimada M, Hisatake K . Heterogeneous nuclear ribonucleoprotein R enhances transcription from the naturally configured c-fos promoter in vitro . Journal of Biological Chemistry . 284 . 23472–80 . 2009 . 35 . 10.1074/jbc.M109.013656 . 19581295 . 2749121 . free .
6. Mourelatos Z, Abel L, Yong J, Kataoka N, Dreyfuss G . SMN interacts with a novel family of hnRNP and spliceosomal proteins . The EMBO Journal . 20 . 19 . 5443–52 . October 2001 . 11574476 . 125643 . 10.1093/emboj/20.19.5443 .
7. Rossoll W, Kröning AK, Ohndorf UM, Steegborn C, Jablonka S, Sendtner M . Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: a role for Smn in RNA processing in motor axons? . Human Molecular Genetics . 11 . 1 . 93–105 . January 2002 . 11773003 . 10.1093/hmg/11.1.93 . free .
8. Wada K, Inoue K, Hagiwara M . Identification of methylated proteins by protein arginine N-methyltransferase 1, PRMT1, with a new expression cloning strategy . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1591 . 1–3 . 1–10 . August 2002 . 12183049 . 10.1016/S0167-4889(02)00202-1 .
9. Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE . A human protein-protein interaction network: a resource for annotating the proteome . Cell . 122 . 6 . 957–68 . September 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . 11858/00-001M-0000-0010-8592-0 . 8235923 . free .
10. Ling SC, Albuquerque CP, Han JS, Lagier-Tourenne C, Tokunaga S, Zhou H, Cleveland DW . ALS-associated mutations in TDP-43 increase its stability and promote TDP-43 complexes with FUS/TLS . Proceedings of the National Academy of Sciences of the United States of America . 107 . 30 . 13318–23 . July 2010 . 20624952 . 10.1073/pnas.1008227107 . 2922163 . 2010PNAS..10713318L . free .