View source for 22ax


==Cryo-EM structure of NSUN2-pre-tRNALeu-SAM==
<StructureSection load='22ax' size='340' side='right'caption='[[22ax]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[22ax]] is a 2 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=22AX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=22AX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=22ax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=22ax OCA], [https://pdbe.org/22ax PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=22ax RCSB], [https://www.ebi.ac.uk/pdbsum/22ax PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=22ax ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/NSUN2_HUMAN NSUN2_HUMAN] Autosomal recessive non-syndromic intellectual disability;Dubowitz syndrome. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/NSUN2_HUMAN NSUN2_HUMAN] RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, PubMed:31199786, PubMed:31358969). Involved in various processes, such as epidermal stem cell differentiation, testis differentiation and maternal to zygotic transition during early development: acts by increasing protein synthesis; cytosine C(5)-methylation promoting tRNA stability and preventing mRNA decay (PubMed:31199786). Methylates cytosine to 5-methylcytosine (m5C) at positions 34 and 48 of intron-containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of tRNA(Gly)(GCC) precursors (PubMed:17071714, PubMed:22995836, PubMed:31199786). tRNA methylation is required generation of RNA fragments derived from tRNAs (tRFs) (PubMed:31199786). Also mediates C(5)-methylation of mitochondrial tRNAs (PubMed:31276587). Catalyzes cytosine C(5)-methylation of mRNAs, leading to stabilize them and prevent mRNA decay: mRNA stabilization involves YBX1 that specifically recognizes and binds m5C-modified transcripts (PubMed:22395603, PubMed:31358969, PubMed:34556860). Cytosine C(5)-methylation of mRNAs also regulates mRNA export: methylated transcripts are specifically recognized by THOC4/ALYREF, which mediates mRNA nucleo-cytoplasmic shuttling (PubMed:28418038). Also mediates cytosine C(5)-methylation of non-coding RNAs, such as vault RNAs (vtRNAs), promoting their processing into regulatory small RNAs (PubMed:23871666). Cytosine C(5)-methylation of vtRNA VTRNA1.1 promotes its processing into small-vault RNA4 (svRNA4) and regulates epidermal differentiation (PubMed:31186410). May act downstream of Myc to regulate epidermal cell growth and proliferation (By similarity). Required for proper spindle assembly and chromosome segregation, independently of its methyltransferase activity (PubMed:19596847).[UniProtKB:Q1HFZ0]<ref>PMID:17071714</ref> <ref>PMID:19596847</ref> <ref>PMID:22395603</ref> <ref>PMID:22995836</ref> <ref>PMID:23871666</ref> <ref>PMID:28418038</ref> <ref>PMID:31186410</ref> <ref>PMID:31199786</ref> <ref>PMID:31276587</ref> <ref>PMID:31358969</ref> <ref>PMID:34556860</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The human RNA m(5)C methyltransferase NSUN2 catalyzes site-specific cytosine methylation across diverse RNA substrates and thereby regulates a wide range of biological and physiological processes. However, the molecular basis by which NSUN2 achieves broad substrate recognition while maintaining catalytic specificity has remained unclear. Here, we determine structures of human NSUN2 in both substrate-free and substrate-bound states using X-ray crystallography and cryo-electron microscopy. Structures of NSUN2 in complex with multiple tRNA substrates reveal a structure-first, sequence-tolerant strategy in which NSUN2 actively remodels tRNA architecture, exposing the buried target cytosine and positioning it within the catalytic pocket for methyl transfer. This recognition strategy enables NSUN2 to accommodate diverse tRNA substrates through a largely conserved interaction interface. Together, our findings define the molecular principles underlying NSUN2-mediated RNA m(5)C modification.

Structure-driven RNA remodeling underlies broad substrate recognition by NSUN2.,Hu Q, Yang W, Yu Y, Yi R, Zhang Y, Duan L, Li F, Zhang K, Gong Q, Li S Sci China Life Sci. 2026 May 26. doi: 10.1007/s11427-026-3373-3. PMID:42258135<ref>PMID:42258135</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 22ax" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hu Q]]
[[Category: Li S]]
[[Category: Yang W]]
[[Category: Zhang K]]