6m1u

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<StructureSection load='6m1u' size='340' side='right'caption='[[6m1u]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
<StructureSection load='6m1u' size='340' side='right'caption='[[6m1u]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6m1u]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M1U OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6M1U FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6m1u]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M1U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M1U FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">METTL16, METT10D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.791&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6m1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m1u OCA], [http://pdbe.org/6m1u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6m1u RCSB], [http://www.ebi.ac.uk/pdbsum/6m1u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6m1u ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6m1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m1u OCA], [https://pdbe.org/6m1u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m1u RCSB], [https://www.ebi.ac.uk/pdbsum/6m1u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m1u ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/MET16_HUMAN MET16_HUMAN]] RNA N6-methyltransferase that methylates adenosine residues of a subset of RNAs and plays a key role in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts (PubMed:28525753). Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6 snRNAs) (PubMed:28525753). In contrast to the METTL3-METTL14 heterodimer, only able to methylate a limited number of RNAs: requires both a 5'UACAGAGAA-3' nonamer sequence and a specific RNA structure (PubMed:28525753). In presence of S-adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and specifically N6-methylates the first hairpin of MAT2A mRNA, impairing MAT2A expression (PubMed:28525753). In S-adenosyl-L-methionine-limiting conditions, binds the 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A (PubMed:28525753). In addition to mRNAs, also able to mediate N6-methylation of U6 small nuclear RNA (U6 snRNA): specifically N6-methylates adenine in position 43 of U6 snRNAs (PubMed:28525753, PubMed:29051200). Also able to bind various lncRNAs (PubMed:29051200). Specifically binds the 3'-end of the MALAT1 long non-coding RNA (PubMed:27872311).<ref>PMID:27872311</ref> <ref>PMID:28525753</ref> <ref>PMID:29051200</ref>
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[https://www.uniprot.org/uniprot/MET16_HUMAN MET16_HUMAN] RNA N6-methyltransferase that methylates adenosine residues of a subset of RNAs and plays a key role in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts (PubMed:28525753). Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6 snRNAs) (PubMed:28525753). In contrast to the METTL3-METTL14 heterodimer, only able to methylate a limited number of RNAs: requires both a 5'UACAGAGAA-3' nonamer sequence and a specific RNA structure (PubMed:28525753). In presence of S-adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and specifically N6-methylates the first hairpin of MAT2A mRNA, impairing MAT2A expression (PubMed:28525753). In S-adenosyl-L-methionine-limiting conditions, binds the 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A (PubMed:28525753). In addition to mRNAs, also able to mediate N6-methylation of U6 small nuclear RNA (U6 snRNA): specifically N6-methylates adenine in position 43 of U6 snRNAs (PubMed:28525753, PubMed:29051200). Also able to bind various lncRNAs (PubMed:29051200). Specifically binds the 3'-end of the MALAT1 long non-coding RNA (PubMed:27872311).<ref>PMID:27872311</ref> <ref>PMID:28525753</ref> <ref>PMID:29051200</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The N6-methyladenosine modification at position 43 (m6A43) of U6 snRNA is catalyzed by METTL16, and is important for the 5'-splice site recognition by U6 snRNA during pre-mRNA splicing. Human METTL16 consists of the N-terminal methyltransferase domain (MTD) and the C-terminal vertebrate conserved region (VCR). While the MTD has an intrinsic property to recognize a specific sequence in the distinct structural context of RNA, the VCR functions have remained uncharacterized. Here, we present structural and functional analyses of the human METTL16 VCR. The VCR increases the affinity of METTL16 toward U6 snRNA, and the conserved basic region in VCR is important for the METTL16-U6 snRNA interaction. The VCR structure is topologically homologous to the C-terminal RNA binding domain, KA1, in U6 snRNA-specific terminal uridylyl transferase 1 (TUT1). A chimera of the N-terminal MTD of METTL16 and the C-terminal KA1 of TUT1 methylated U6 snRNA more efficiently than the MTD, indicating the functional conservation of the VCR and KA1 for U6 snRNA biogenesis. The VCR interacts with the internal stem-loop (ISL) within U6 snRNA, and this interaction would induce the conformational rearrangement of the A43-containing region of U6 snRNA, thereby modifying the RNA structure to become suitable for productive catalysis by the MTD. Therefore, the MTD and VCR in METTL16 cooperatively facilitate the m6A43 U6 snRNA modification.
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Mechanistic insights into m6A modification of U6 snRNA by human METTL16.,Aoyama T, Yamashita S, Tomita K Nucleic Acids Res. 2020 May 21;48(9):5157-5168. doi: 10.1093/nar/gkaa227. PMID:32266935<ref>PMID:32266935</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6m1u" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Aoyama, T]]
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[[Category: Aoyama T]]
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[[Category: Tomita, K]]
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[[Category: Tomita K]]
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[[Category: Yamashita, S]]
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[[Category: Yamashita S]]
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[[Category: Methyltransferase]]
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[[Category: Rna binding protein]]
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Current revision

Crystal structure of the vertebrate conserved region (VCR) of human METTL16

PDB ID 6m1u

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