| Structural highlights
Function
[TDRD1_MOUSE] Plays a central role during spermatogenesis by participating in the repression transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Required for the localization of Piwi proteins to the meiotic nuage. Involved in the piRNA metabolic process by ensuring the entry of correct transcripts into the normal piRNA pool and limiting the entry of cellular transcripts into the piRNA pathway. May act by allowing the recruitment of piRNA biogenesis or loading factors that ensure the correct entry of transcripts and piRNAs into Piwi proteins.[1] [2] [3]
Publication Abstract from PubMed
Piwi-interacting RNAs (piRNAs) are small noncoding RNAs expressed in the germline of animals. They associate with Argonaute proteins of the Piwi subfamily, forming ribonucleoprotein complexes that are involved in maintaining genome integrity. The N-terminal region of some Piwi proteins contains symmetrically dimethylated arginines. This modification is thought to enable recruitment of Tudor domain-containing proteins (TDRDs), which might serve as platforms mediating interactions between various proteins in the piRNA pathway. We measured the binding affinity of the four individual extended Tudor domains (TDs) of murine TDRD1 protein for three different methylarginine-containing peptides from murine Piwi protein MILI. The results show a preference of TD2 and TD3 for consecutive MILI peptides, whereas TD4 and TD1 have, respectively, lower and very weak affinity for any peptide. The affinity of TD1 for methylarginine peptides can be restored by a single-point mutation back to the consensus aromatic cage sequence. These observations were confirmed by pull-down experiments with endogenous Piwi and Piwi-associated proteins. The crystal structure of TD3 bound to a methylated MILI peptide shows an unexpected orientation of the bound peptide, with additional contacts of nonmethylated residues being made outside of the aromatic cage, consistent with solution NMR titration experiments. Finally, the molecular envelope of the four tandem Tudor domains of TDRD1, derived from small angle scattering data, reveals a flexible, elongated shape for the protein. Overall, the results show that TDRD1 can accommodate different peptides from different proteins, and can therefore act as a scaffold protein for complex assembly in the piRNA pathway.
The multiple Tudor domain-containing protein TDRD1 is a molecular scaffold for mouse Piwi proteins and piRNA biogenesis factors.,Mathioudakis N, Palencia A, Kadlec J, Round A, Tripsianes K, Sattler M, Pillai RS, Cusack S RNA. 2012 Sep 20. PMID:22996915[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chuma S, Hosokawa M, Kitamura K, Kasai S, Fujioka M, Hiyoshi M, Takamune K, Noce T, Nakatsuji N. Tdrd1/Mtr-1, a tudor-related gene, is essential for male germ-cell differentiation and nuage/germinal granule formation in mice. Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):15894-9. Epub 2006 Oct 12. PMID:17038506 doi:http://dx.doi.org/10.1073/pnas.0601878103
- ↑ Reuter M, Chuma S, Tanaka T, Franz T, Stark A, Pillai RS. Loss of the Mili-interacting Tudor domain-containing protein-1 activates transposons and alters the Mili-associated small RNA profile. Nat Struct Mol Biol. 2009 Jun;16(6):639-46. doi: 10.1038/nsmb.1615. Epub 2009 May, 24. PMID:19465913 doi:http://dx.doi.org/10.1038/nsmb.1615
- ↑ Vagin VV, Wohlschlegel J, Qu J, Jonsson Z, Huang X, Chuma S, Girard A, Sachidanandam R, Hannon GJ, Aravin AA. Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members. Genes Dev. 2009 Aug 1;23(15):1749-62. doi: 10.1101/gad.1814809. Epub 2009 Jul 7. PMID:19584108 doi:http://dx.doi.org/10.1101/gad.1814809
- ↑ Mathioudakis N, Palencia A, Kadlec J, Round A, Tripsianes K, Sattler M, Pillai RS, Cusack S. The multiple Tudor domain-containing protein TDRD1 is a molecular scaffold for mouse Piwi proteins and piRNA biogenesis factors. RNA. 2012 Sep 20. PMID:22996915 doi:http://dx.doi.org/10.1261/rna.034181.112
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