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RNA-modifying proteins

A closer look at RMPs: an emerging major target space for drug discovery

Discoveries at the forefront of biology have unveiled cellular control mechanisms that determine which RNA transcripts are translated into cell proteins, and when. This new area of biology depends on an assembly of proteins involved in different aspects of RNA modifications, collectively referred to as the RNA-modifying proteins (RMPs).

The central dogma of molecular biology follows the transcription of DNA to messenger RNA (mRNA) and the translation of mRNA to proteins. Epigenetic modifications of chromatin gate transcription, and in an analogous way epitranscriptomics gate translation through RNA modifications. Finally, substantial augmentation of the cellular protein repertoire is achieved by post-translational modifications (PTMs) of proteins. Though illustrated here with modifications to mRNA, modifications are also ubiquitous to other RNA forms (including tRNA, rRNA, lncRNAs, snoRNAs, snRNAs, and circRNAs).

Akin to the way that epigenetics revolutionized our understanding of gene transcription to mRNA as a gated process, recent studies have shown that the process of mRNA translation to proteins, which, in many cases, ultimately determines cell fate, is similarly gated and controlled by covalent modifications at selective sites within specific nucleotides of RNA.

How modification is integrated into successive stages in the journey from DNA to protein.

Nucleotide bases are dynamically and reversibly modifiable, as part of the normal lifecycle of RNA molecules. However, certain cancers have been associated with increased levels of certain RNA-modifying proteins leading to ‘signature’ modifications that support tumor growth and survival.

The enzymes that place covalent modifications on RNA molecules—including changes to the RNA base structure, those that remove these covalent modifications and the proteins that recognize and bind selectively to the modified versions of RNA—are collectively referred to as RMPs.

RMPs consist of three classes of proteins: Readers, Writers and Erasers.

writers readers erasers

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