Laboratoire de Chimie des Processus Biologiques, CNRS-UMR 8229, Collège De France, Université Pierre et marie Curie, 11 Place Marcelin Berthelot, 75231 Paris Cedex 05, France. Electronic address:
Published: October 2017
AI Article Synopsis
Article Abstract
RNAs molecules fulfill key roles in the expression and regulation of the genetic information stored within the DNA chromosomes. In addition to the four canonical bases, U, C, A and G, RNAs harbor various chemically modified derivatives which are generated post-transcriptionally by specific enzymes acting directly at the polymer level. More than one hundred naturally occurring modified nucleosides have been identified to date, the largest number of which is found in tRNAs and rRNA. This remarkable biochemical process produces widely diversified RNAs further expanding the functional repertoires of these nucleic acids. Interestingly, several RNA-modifying enzymes use a flavin bioorganic molecule as a coenzyme in RNA modification pathways. Some of these reactions are simple while others are extremely complex using challenging chemistry orchestrated by large flavoenzymatic systems. In this review, we summarize recent knowledges on the flavin-dependent RNA-modifying enzymes and discuss the relevance of their activity within a cellular context.
Neurodegenerative disorders encompass a group of age-related conditions characterized by the gradual decline in both the structure and functionality of the central nervous system (CNS). RNA modifications, arising from the epitranscriptome or RNA-modifying protein mutations, have recently been observed to contribute significantly to neurodegenerative disorders. Specific modifications like N6-methyladenine (m6A), N1-methyladenine (m1A), 5-methylcytosine (m5C), pseudouridine and adenosine-to-inosine (A-to-I) play key roles, with their regulators serving as crucial therapeutic targets.
RNA-modifying enzymes have recently garnered considerable attention due to their relevance in cancer biology, identifying them as potential targets for novel therapeutic intervention. THUMPD3 was recently identified as an RNA methyltransferase catalysing N2-methylguanosine (m2G) within certain tRNAs. In this study, we unveil a novel role for THUMPD3 in lung cancer cells.
Background: RNA modifications, a central aspect of epitranscriptomics, add a regulatory layer to gene expression by modifying RNA function without altering nucleotide sequences. These modifications play vital roles across RNA species, influencing RNA stability, translation, and interaction dynamics, and are regulated by specific enzymes that add, remove, and interpret these chemical marks.
Objective: This review examines the role of aberrant RNA modifications in cancer progression, exploring their potential as diagnostic and prognostic biomarkers and as therapeutic targets.
* Analysis of protein interactions revealed that Ssr1238 binds mainly to RNase P RNA and its associated protein RnpA, as well as other transcripts linked to cell division and RNA maturation.
* The findings suggest that Ssr1238 plays a crucial role in coordinating RNA processes and nitrogen metabolism, potentially expanding the known functions of similar proteins in cyanobacteria.
In recent years, RNA-modifying enzymes have gained significant attention due to their impact on critical RNA-based processes and, consequently, human pathology. However, identifying sites of modifications throughout the transcriptome remains challenging largely due to the lack of accurate and sensitive detection technologies. Recently, we described PhOxi-seq as a method capable of confirming known sites of mG within abundant classes of RNA, namely, purified rRNA and purified tRNA.
