5wu4

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Crystal structure of human Tut1 bound with MgATP, form II

Structural highlights

5wu4 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.8Å
Ligands:ATP, CL, MG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

STPAP_HUMAN Poly(A) polymerase that creates the 3'-poly(A) tail of specific pre-mRNAs. Localizes to nuclear speckles together with PIP5K1A and mediates polyadenylation of a select set of mRNAs, such as HMOX1. In addition to polyadenylation, it is also required for the 3'-end cleavage of pre-mRNAs: binds to the 3'UTR of targeted pre-mRNAs and promotes the recruitment and assembly of the CPSF complex on the 3'UTR of pre-mRNAs. In addition to adenylyltransferase activity, also has uridylyltransferase activity. However, the ATP ratio is higher than UTP in cells, suggesting that it functions primarily as a poly(A) polymerase. Acts as a specific terminal uridylyltransferase for U6 snRNA in vitro: responsible for a controlled elongation reaction that results in the restoration of the four 3'-terminal UMP-residues found in newly transcribed U6 snRNA. Not involved in replication-dependent histone mRNA degradation.[1] [2] [3]

Publication Abstract from PubMed

The terminal uridylyltransferase, TUT1, builds or repairs the 3'-oligo-uridylylated tail of U6 snRNA. The 3'-oligo-uridylylated tail is the Lsm-binding site for U4/U6 di-snRNP formation and U6 snRNA recycling for pre-mRNA splicing. Here, we report crystallographic and biochemical analyses of human TUT1, which revealed the mechanisms for the specific uridylylation of the 3'-end of U6 snRNA by TUT1. The O2 and O4 atoms of the UTP base form hydrogen bonds with the conserved His and Asn in the catalytic pocket, respectively, and TUT1 preferentially incorporates UMP onto the 3'-end of RNAs. TUT1 recognizes the entire U6 snRNA molecule by its catalytic domains, N-terminal RNA-recognition motifs and a previously unidentified C-terminal RNA-binding domain. Each domain recognizes specific regions within U6 snRNA, and the recognition is coupled with the domain movements and U6 snRNA structural changes. Hence, TUT1 functions as the U6 snRNA-specific terminal uridylyltransferase required for pre-mRNA splicing.

Crystal structures of U6 snRNA-specific terminal uridylyltransferase.,Yamashita S, Takagi Y, Nagaike T, Tomita K Nat Commun. 2017 Jun 7;8:15788. doi: 10.1038/ncomms15788. PMID:28589955[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ Trippe R, Guschina E, Hossbach M, Urlaub H, Luhrmann R, Benecke BJ. Identification, cloning, and functional analysis of the human U6 snRNA-specific terminal uridylyl transferase. RNA. 2006 Aug;12(8):1494-504. Epub 2006 Jun 21. PMID:16790842 doi:http://dx.doi.org/rna.87706
  2. ↑ Mellman DL, Gonzales ML, Song C, Barlow CA, Wang P, Kendziorski C, Anderson RA. A PtdIns4,5P2-regulated nuclear poly(A) polymerase controls expression of select mRNAs. Nature. 2008 Feb 21;451(7181):1013-7. doi: 10.1038/nature06666. PMID:18288197 doi:http://dx.doi.org/10.1038/nature06666
  3. ↑ Laishram RS, Anderson RA. The poly A polymerase Star-PAP controls 3'-end cleavage by promoting CPSF interaction and specificity toward the pre-mRNA. EMBO J. 2010 Dec 15;29(24):4132-45. doi: 10.1038/emboj.2010.287. Epub 2010 Nov, 19. PMID:21102410 doi:http://dx.doi.org/10.1038/emboj.2010.287
  4. ↑ Yamashita S, Takagi Y, Nagaike T, Tomita K. Crystal structures of U6 snRNA-specific terminal uridylyltransferase. Nat Commun. 2017 Jun 7;8:15788. doi: 10.1038/ncomms15788. PMID:28589955 doi:http://dx.doi.org/10.1038/ncomms15788

Contents


PDB ID 5wu4

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OCA

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