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Substrate selectivity of the human RNA m5C methyltransferase NSUN2

Nature·Jacob Canepa·3 days ago
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Main RNAs are decorated with various chemical modifications that determine their fate, and specific m 5 C deposition is important for regulating gene expression necessary for cell proliferation and differentiation, development, stress response and immunity 3 , 4 . The NOP2/Sun (NSUN) family of methyltransferases add m 5 C modifications to RNAs 5 , which can then be detected by reader proteins to regulate RNA function, transport or stability and also be removed by TET enzymes or ALKBH1 (refs.  6 , 7 , 8 , 9 ). Thus, m 5 C is a dynamic epitranscriptomic modification that provides a handle for regulating RNAs post-transcriptionally. NSUN2 is the primary m 5 C writer for mRNAs, and its dysregulation has been implicated in numerous human diseases 10 , 11 , 12 , 13 . Loss-of-function mutations in NSUN2 cause intellectual disability and Dubowitz-like syndrome, as NSUN2 is important for neural circuit formation and synaptic function 14 , 15 , 16 , 17 .…

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