HNRPD explained

Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) also known as AU-rich element RNA-binding protein 1 (AUF1) is a protein that in humans is encoded by the HNRNPD gene.^{[1] [2]} Alternative splicing of this gene results in four transcript variants.

Function

This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are nucleic acid binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). The interaction sites on the RNA are frequently biased towards particular sequence motifs.^[3] 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 two repeats of quasi-RRM domains that bind to RNAs. It localizes to both the nucleus and the cytoplasm. This protein is implicated in the regulation of mRNA stability.

Interactions

HnRNP D has been shown to interact with SAFB^[4] and Hsp27.^[5] It also has been reported to interact with mRNAs such as Mef2c mRNA.^[6]

References

Further reading

• Tay N, Chan SH, Ren EC . Identification and cloning of a novel heterogeneous nuclear ribonucleoprotein C-like protein that functions as a transcriptional activator of the hepatitis B virus enhancer II . J. Virol. . 66 . 12 . 6841–8 . 1992 . 1433497 . 240284 . 10.1128/JVI.66.12.6841-6848.1992.
• Lahiri DK, Thomas JO . A cDNA clone of the hnRNP C proteins and its homology with the single-stranded DNA binding protein UP2 . Nucleic Acids Res. . 14 . 10 . 4077–4094 . 1986 . 3754960 . 339847 . 10.1093/nar/14.10.4077 .
• Kajita Y, Nakayama J, Aizawa M, Ishikawa F . The UUAG-specific RNA binding protein, heterogeneous nuclear ribonucleoprotein D0. Common modular structure and binding properties of the 2xRBD-Gly family . J. Biol. Chem. . 270 . 38 . 22167–75 . 1995 . 7673195 . 10.1074/jbc.270.38.22167 . free .
• Zhang W, Wagner BJ, Ehrenman K, Schaefer AW, DeMaria CT, Crater D, DeHaven K, Long L, Brewer G . Purification, characterization, and cDNA cloning of an AU-rich element RNA-binding protein, AUF1 . Mol. Cell. Biol. . 13 . 12 . 7652–65 . December 1993 . 8246982 . 364837 . 10.1128/MCB.13.12.7652.
• Wagner BJ, Long L, Rao PN, Pettenati MJ, Brewer G . Localization and physical mapping of genes encoding the A+U-rich element RNA-binding protein AUF1 to human chromosomes 4 and X . Genomics . 34 . 2 . 219–22 . June 1996 . 8661052 . 10.1006/geno.1996.0269 .
• Kiledjian M, DeMaria CT, Brewer G, Novick K . Identification of AUF1 (heterogeneous nuclear ribonucleoprotein D) as a component of the alpha-globin mRNA stability complex . Mol. Cell. Biol. . 17 . 8 . 4870–6 . 1997 . 9234743 . 232339 . 10.1128/MCB.17.8.4870.
• Wagner BJ, DeMaria CT, Sun Y, Wilson GM, Brewer G . Structure and genomic organization of the human AUF1 gene: alternative pre-mRNA splicing generates four protein isoforms . Genomics . 48 . 2 . 195–202 . March 1998 . 9521873 . 10.1006/geno.1997.5142 .
• Siomi MC, Fromont M, Rain JC, Wan L, Wang F, Legrain P, Dreyfuss G . Functional conservation of the transportin nuclear import pathway in divergent organisms . Mol. Cell. Biol. . 18 . 7 . 4141–8 . July 1998 . 9632798 . 108998 . 10.1128/MCB.18.7.4141.
• Tolnay M, Vereshchagina LA, Tsokos GC . Heterogeneous nuclear ribonucleoprotein D0B is a sequence-specific DNA-binding protein . Biochem. J. . 338 . 2 . 417–25 . 1999 . 10024518 . 1220068 . 10.1042/0264-6021:3380417 .
• Nagata T, Kurihara Y, Matsuda G, Saeki J, Kohno T, Yanagida Y, Ishikawa F, Uesugi S, Katahira M . Structure and interactions with RNA of the N-terminal UUAG-specific RNA-binding domain of hnRNP D0 . J. Mol. Biol. . 287 . 2 . 221–37 . March 1999 . 10080887 . 10.1006/jmbi.1999.2616 .
• Laroia G, Cuesta R, Brewer G, Schneider RJ . Control of mRNA decay by heat shock-ubiquitin-proteasome pathway . Science . 284 . 5413 . 499–502 . 1999 . 10205060 . 10.1126/science.284.5413.499 . 1999Sci...284..499L .
• Blaxall BC, Dwyer-Nield LD, Bauer AK, Bohlmeyer TJ, Malkinson AM, Port JD . Differential expression and localization of the mRNA binding proteins, AU-rich element mRNA binding protein (AUF1) and Hu antigen R (HuR), in neoplastic lung tissue . Mol. Carcinog. . 28 . 2 . 76–83 . June 2000 . 10900464 . 10.1002/1098-2744(200006)28:2<76::AID-MC3>3.0.CO;2-0 . 25180996 .
• Moraes KC, Quaresma AJ, Maehnss K, Kobarg J . Identification and characterization of proteins that selectively interact with isoforms of the mRNA binding protein AUF1 (hnRNP D) . Biol. Chem. . 384 . 1 . 25–37 . January 2003 . 12674497 . 10.1515/BC.2003.004 . 30993043 .
• Arao Y, Kuriyama R, Kayama F, Kato S . A nuclear matrix-associated factor, SAF-B, interacts with specific isoforms of AUF1/hnRNP D . Arch. Biochem. Biophys. . 380 . 2 . 228–236 . 2000 . 10933876 . 10.1006/abbi.2000.1938 .
• Grosset C, Chen CY, Xu N, Sonenberg N, Jacquemin-Sablon H, Shyu AB . A mechanism for translationally coupled mRNA turnover: interaction between the poly(A) tail and a c-fos RNA coding determinant via a protein complex . Cell . 103 . 1 . 29–40 . September 2000 . 11051545 . 10.1016/S0092-8674(00)00102-1 . 18135412 . free .
• Katahira M, Miyanoiri Y, Enokizono Y, Matsuda G, Nagata T, Ishikawa F, Uesugi S . Structure of the C-terminal RNA-binding domain of hnRNP D0 (AUF1), its interactions with RNA and DNA, and change in backbone dynamics upon complex formation with DNA . J. Mol. Biol. . 311 . 5 . 973–88 . August 2001 . 11531333 . 10.1006/jmbi.2001.4862 .
• Lapucci A, Donnini M, Papucci L, Witort E, Tempestini A, Bevilacqua A, Nicolin A, Brewer G, Schiavone N, Capaccioli S . AUF1 Is a bcl-2 A + U-rich element-binding protein involved in bcl-2 mRNA destabilization during apoptosis . J. Biol. Chem. . 277 . 18 . 16139–46 . May 2002 . 11856759 . 10.1074/jbc.M201377200 . free .
• Tolnay M, Juang YT, Tsokos GC . Protein kinase A enhances, whereas glycogen synthase kinase-3 beta inhibits, the activity of the exon 2-encoded transactivator domain of heterogeneous nuclear ribonucleoprotein D in a hierarchical fashion . Biochem. J. . 363 . Pt 1 . 127–36 . 2002 . 11903055 . 1222459 . 10.1042/0264-6021:3630127 .
• Pioli PA, Hamilton BJ, Connolly JE, Brewer G, Rigby WF . Lactate dehydrogenase is an AU-rich element-binding protein that directly interacts with AUF1 . J. Biol. Chem. . 277 . 38 . 35738–45 . September 2002 . 12107167 . 10.1074/jbc.M204002200 . free .
• Shchors K, Yehiely F, Kular RK, Kotlo KU, Brewer G, Deiss LP . Cell death inhibiting RNA (CDIR) derived from a 3'-untranslated region binds AUF1 and heat shock protein 27 . J. Biol. Chem. . 277 . 49 . 47061–72 . December 2002 . 12356764 . 10.1074/jbc.M202272200 . free .

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human Heterogeneous nuclear ribonucleoprotein D0 (HNRPD)

Notes and References

1. Dempsey LA, Li MJ, DePace A, Bray-Ward P, Maizels N . The human HNRPD locus maps to 4q21 and encodes a highly conserved protein . Genomics . 49 . 3 . 378–384 . August 1998 . 9615222 . 10.1006/geno.1998.5237 . free .
2. Web site: Entrez Gene: HNRPD heterogeneous nuclear ribonucleoprotein D (AU-rich element RNA binding protein 1, 37kDa).
3. Mazan-Mamczarz K, Kuwano Y, Zhan M, White EJ, Martindale JL, Lal A, Gorospe M . Identification of a signature motif in target mRNAs of RNA-binding protein AUF1. . Nucleic Acids Research . 37 . 1 . 204–14 . Jan 2009 . 19033365 . 10.1093/nar/gkn929 . 2615618.
4. Arao Y, Kuriyama R, Kayama F, Kato S . A nuclear matrix-associated factor, SAF-B, interacts with specific isoforms of AUF1/hnRNP D . Arch. Biochem. Biophys. . 380 . 2 . 228–36 . August 2000 . 10933876 . 10.1006/abbi.2000.1938 .
5. Sinsimer KS, Gratacós FM, Knapinska AM, Lu J, Krause CD, Wierzbowski AV, Maher LR, Scrudato S, Rivera YM, Gupta S, Turrin DK, De La Cruz MP, Pestka S, Brewer G . Chaperone Hsp27, a novel subunit of AUF1 protein complexes, functions in AU-rich element-mediated mRNA decay . Mol. Cell. Biol. . 28 . 17 . 5223–37 . September 2008 . 18573886 . 2519747 . 10.1128/MCB.00431-08 .
6. Panda AC, Abdelmohsen K, Yoon JH, Martindale JL, Yang X, Curtis J, Mercken EM, Chenette DM, Zhang Y, Schneider RJ, Becker KG, de Cabo R, Gorospe M . Aug 2014 . RNA-binding protein AUF1 promotes myogenesis by regulating MEF2C expression levels . Mol Cell Biol . 34 . 16. 3106–19 . 10.1128/MCB.00423-14 . 24891619 . 4135590.