Title: Biosynthesis and Functions of Modified Nucleosides in Eukaryotic mRNA
Abstract: This chapter focuses on the sequence-specific methylation of internal adenosine residues to form N6-methyladenosine. It talks about nucleosides modifications present in cellular mRNA; the nucleoside modifications present in virion RNA and viral mRNA are also be discussed because of the nearly complete overlap of the spectrum of modifications present. Lower eukaryotes such as yeast and Neurospora contain only cap 0. Collectively, these cap methylation events account for the presence of most of the nucleoside modifications in eukaryotic mRNA, namely, 7-methylguanine (m7G), all four 2'-O-methylnucleosides (Nm), and N6,2'-Odimethyl-adenosine (m6Am). Three modified nucleosides have been reported within internal regions of eukaryotic mRNA: N6methyladenosine (m6A), 5-methylcytidine (m5C), and inosine. A study examined short (20 nucleotide) synthetic RNA substrates and confirmed that the in vitro specificity closely paralleled the frequency with which sequences are methylated in vivo as originally described by Schibler. This study was extended by evaluating an additional two m6A sites in a similar fashion. Camper and his coworkers utilized an inhibitor, S-tubericidinylhomocysteine (STH), which is a structural analog of S-adenosylmethionine (SAM) and a potent inhibitor of SAM-dependent methyltransferases. In this study, the effects of the inhibitor on cap methylation and internal methylation were closely monitored. Posttranscriptional modification of nucleosides within mRNA molecules is an integral aspect of premRNA processing. These modifications are characteristic of eukaryotic mRNA only; no equivalent nucleotide modifications have been found in any of the prokaryotic mRNAs characterized so far.
Publication Year: 2014
Publication Date: 2014-04-30
Language: en
Type: book-chapter
Indexed In: ['crossref']
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Cited By Count: 13
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