| Structural highlights
Function
[TDRD3_HUMAN] Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci. In cytoplasm, may play a role in the assembly and/or disassembly of mRNA stress granules and in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins.[1] [2] [3] [RPB1_HUMAN] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Forms the polymerase active center together with the second largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB1 is part of the core element with the central large cleft, the clamp element that moves to open and close the cleft and the jaws that are thought to grab the incoming DNA template. At the start of transcription, a single stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol II. A bridging helix emanates from RPB1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol II by acting as a ratchet that moves the RNA-DNA hybrid through the active site by switching from straight to bent conformations at each step of nucleotide addition. During transcription elongation, Pol II moves on the template as the transcript elongates. Elongation is influenced by the phosphorylation status of the C-terminal domain (CTD) of Pol II largest subunit (RPB1), which serves as a platform for assembly of factors that regulate transcription initiation, elongation, termination and mRNA processing. Acts as a RNA-dependent RNA polymerase when associated with small delta antigen of Hepatitis delta virus, acting both as a replicate and transcriptase for the viral RNA circular genome.[4] [5]
Publication Abstract from PubMed
Asymmetric dimethylarginine (aDMA) marks are placed on histones and the C-terminal domain (CTD) of RNA Polymerase II (RNAP II) and serve as a signal for recruitment of appropriate transcription and processing factors in coordination with transcription cycle. In contrast to other Tudor domain-containing proteins, Tudor domain-containing protein 3 (TDRD3) associates selectively with the aDMA marks but not with other methylarginine motifs. Here, we report the solution structure of the Tudor domain of TDRD3 bound to the asymmetrically dimethylated CTD. The structure and mutational analysis provide a molecular basis for how TDRD3 recognizes the aDMA mark. The unique aromatic cavity of the TDRD3 Tudor domain with a tyrosine in position 566 creates a selectivity filter for the aDMA residue. Our work contributes to the understanding of substrate selectivity rules of the Tudor aromatic cavity, which is an important structural motif for reading of methylation marks.
Recognition of asymmetrically dimethylated arginine by TDRD3.,Sikorsky T, Hobor F, Krizanova E, Pasulka J, Kubicek K, Stefl R Nucleic Acids Res. 2012 Dec 1;40(22):11748-55. doi: 10.1093/nar/gks929. Epub 2012, Oct 12. PMID:23066109[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Goulet I, Boisvenue S, Mokas S, Mazroui R, Cote J. TDRD3, a novel Tudor domain-containing protein, localizes to cytoplasmic stress granules. Hum Mol Genet. 2008 Oct 1;17(19):3055-74. doi: 10.1093/hmg/ddn203. Epub 2008 Jul , 15. PMID:18632687 doi:10.1093/hmg/ddn203
- ↑ Cote J, Richard S. Tudor domains bind symmetrical dimethylated arginines. J Biol Chem. 2005 Aug 5;280(31):28476-83. Epub 2005 Jun 6. PMID:15955813 doi:M414328200
- ↑ Yang Y, Lu Y, Espejo A, Wu J, Xu W, Liang S, Bedford MT. TDRD3 is an effector molecule for arginine-methylated histone marks. Mol Cell. 2010 Dec 22;40(6):1016-23. doi: 10.1016/j.molcel.2010.11.024. PMID:21172665 doi:10.1016/j.molcel.2010.11.024
- ↑ Kershnar E, Wu SY, Chiang CM. Immunoaffinity purification and functional characterization of human transcription factor IIH and RNA polymerase II from clonal cell lines that conditionally express epitope-tagged subunits of the multiprotein complexes. J Biol Chem. 1998 Dec 18;273(51):34444-53. PMID:9852112
- ↑ Chang J, Nie X, Chang HE, Han Z, Taylor J. Transcription of hepatitis delta virus RNA by RNA polymerase II. J Virol. 2008 Feb;82(3):1118-27. Epub 2007 Nov 21. PMID:18032511 doi:http://dx.doi.org/10.1128/JVI.01758-07
- ↑ Sikorsky T, Hobor F, Krizanova E, Pasulka J, Kubicek K, Stefl R. Recognition of asymmetrically dimethylated arginine by TDRD3. Nucleic Acids Res. 2012 Dec 1;40(22):11748-55. doi: 10.1093/nar/gks929. Epub 2012, Oct 12. PMID:23066109 doi:http://dx.doi.org/10.1093/nar/gks929
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