Role of RNA methyltransferases in tissue renewal and pathology

Abstract

Over the last five decades more than 100 types of RNA modifications have been identified in organism of all kingdoms of life, yet their function and biological relevance remain largely elusive. The recent development of transcriptome-wide techniques to detect RNA modifications such as N6-methyladenosine (m6A) and 5-methylcytidine (m5C) has not only created a new field of research ‘the epitranscriptome’ but also featured essential regulatory roles of RNA methylation in a wide range of fundamental cellular processes. Here, we discuss the current knowledge of m6A and m5C RNA methylation pathways and summarize how they impact normal tissues and contribute to human disease.

Statistically robust methylation calling for whole-transcriptome bisulfite sequencing reveals distinct methylation patterns for mouse RNAs

“…Furthermore, m5C is also a widely conserved modification of rRNA, where it is implied in the quality control of ribosome biogenesis (Sharma et al 2013;Bourgeois et al 2015;Schosserer et al 2015). These processes have been associated with a variety of human diseases (Blanco and Frye 2014). m5C in RNA can be reliably detected using radioactive labeling and thin-layer chromatography (Hengesbach et al 2008).…”

RNA methylation in lymphoid malignancies

“…While the m 6 A modification has been shown to be associated with different diseases [4,17,18] , the m 6 A methylation status in lymphoid malignancies is unknown. To determine whether mRNA from normal human B cells and from malignant B cells have variable total m 6 A content, mRNA was directly isolated from GM06990 (normal B cells) and B cell lymphoma subtypes (DLBCL (DL), Raji (BL) and NALM6 (pre-B ALL cells from a relapsed patient).…”

tRN-A-RS Acts As Biomarker for Cancer and Other Diseases

“…Additionally, a homoplasmic mutation A4435G (A37 in the anticodon loop of tRNA) considerably decreases the level of the (mt)tRNA Met(CAU) and reduces translation in mitochondria, and is considered to be an inherent risk factor for hypertension [48]. (mt)tRNA mutations are catalogued in variety of databases, such as MITOMAP, and Online Mendelian Inheritance in Man, OMIM [49,50].…”

“…In eukaryotes, more than 100 chemically diverse modifications have been identified so far, many of which are conserved among organisms (see MODOMICS database) and between tRNAs encoded in the nuclear or organelle genomes. Generally, positions 9,26,32,34,37,38,48,49,50 of tRNA are affected most by different modifications that ultimately lead to diseases [108]. Conserved modifications across all domains of life underscore their biological importance.…”