6du4

From Proteopedia

Crystal structure of hMettl16 catalytic domain in complex with MAT2A 3'UTR hairpin 1

PDB ID 6du4

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Structural highlights

6du4 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 1.7Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).^[1] ^[2] ^[3]

References

↑ Brown JA, Kinzig CG, DeGregorio SJ, Steitz JA. Methyltransferase-like protein 16 binds the 3'-terminal triple helix of MALAT1 long noncoding RNA. Proc Natl Acad Sci U S A. 2016 Dec 6;113(49):14013-14018. doi:, 10.1073/pnas.1614759113. Epub 2016 Nov 21. PMID:27872311 doi:http://dx.doi.org/10.1073/pnas.1614759113
↑ Pendleton KE, Chen B, Liu K, Hunter OV, Xie Y, Tu BP, Conrad NK. The U6 snRNA m(6)A Methyltransferase METTL16 Regulates SAM Synthetase Intron Retention. Cell. 2017 May 18;169(5):824-835.e14. doi: 10.1016/j.cell.2017.05.003. PMID:28525753 doi:http://dx.doi.org/10.1016/j.cell.2017.05.003
↑ Warda AS, Kretschmer J, Hackert P, Lenz C, Urlaub H, Hobartner C, Sloan KE, Bohnsack MT. Human METTL16 is a N(6)-methyladenosine (m(6)A) methyltransferase that targets pre-mRNAs and various non-coding RNAs. EMBO Rep. 2017 Nov;18(11):2004-2014. doi: 10.15252/embr.201744940. Epub 2017 Oct , 19. PMID:29051200 doi:http://dx.doi.org/10.15252/embr.201744940