RNA cytosine C

Definition:

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). 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. 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. tRNA methylation is required generation of RNA fragments derived from tRNAs (tRFs). Also mediates C(5)-methylation of mitochondrial tRNAs. 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. Cytosine C(5)-methylation of mRNAs also regulates mRNA export: methylated transcripts are specifically recognized by THOC4/ALYREF, which mediates mRNA nucleo-cytoplasmic shuttling. Also mediates cytosine C(5)-methylation of non-coding RNAs, such as vault RNAs (vtRNAs), promoting their processing into regulatory small RNAs. Cytosine C(5)-methylation of vtRNA VTRNA1.1 promotes its processing into small-vault RNA4 (svRNA4) and regulates epidermal differentiation. 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.

References:

[1]. Sylvie Auxilien, et al. The human tRNA m (5) C methyltransferase Misu is multisite-specific. RNA Biol. 2012 Nov;9(11):1331-8. [Content Brief]

[2]. Nikoletta A Gkatza, et al. Cytosine-5 RNA methylation links protein synthesis to cell metabolism. PLoS Biol. 2019 Jun 14;17(6):e3000297. [Content Brief]

[3]. Xin Chen, et al. 5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs. Nat Cell Biol. 2019 Aug;21(8):978-990. [Content Brief]

[4]. Lindsey Van Haute, et al. NSUN2 introduces 5-methylcytosines in mammalian mitochondrial tRNAs. Nucleic Acids Res. 2019 Sep 19;47(16):8720-8733. [Content Brief]

[5]. Wei Dai, et al. Activity-based RNA-modifying enzyme probing reveals DUS3L-mediated dihydrouridylation. Nat Chem Biol. 2021 Nov;17(11):1178-1187. [Content Brief]

[6]. Xin Yang, et al. 5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and ALYREF as an m5C reader. Cell Res. 2017 May;27(5):606-625. [Content Brief]

[7]. Shobbir Hussain, et al. The nucleolar RNA methyltransferase Misu (NSun2) is required for mitotic spindle stability. J Cell Biol. 2009 Jul 13;186(1):27-40. [Content Brief]

[8]. Xiaotian Zhang, et al. The tRNA methyltransferase NSun2 stabilizes p16INK⁴ mRNA by methylating the 3'-untranslated region of p16. Nat Commun. 2012 Mar 6;3:712. [Content Brief]

[9]. Shobbir Hussain, et al. NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs. Cell Rep. 2013 Jul 25;4(2):255-61. [Content Brief]

[10]. Abdulrahim A Sajini, et al. Loss of 5-methylcytosine alters the biogenesis of vault-derived small RNAs to coordinate epidermal differentiation. Nat Commun. 2019 Jun 11;10(1):2550. [Content Brief]

[11]. Bartosz Brzezicha, et al. Identification of human tRNA:m5C methyltransferase catalysing intron-dependent m5C formation in the first position of the anticodon of the pre-tRNA Leu (CAA). Nucleic Acids Res. 2006;34(20):6034-43. [Content Brief]

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