Abstract

It has been known for a few decades that transcripts can be marked by dozens of different modifications. Yet, we are just at the beginning of charting these marks and understanding their functional impact. High-quality methods were developed for the profiling of some of these marks, and approaches to finely study their impact on specific phases of the RNA life-cycle are available, including RNA metabolic labeling. Thanks to these improvements, the most abundant marks, including N6-methyladenosine, are emerging as important determinants of the fate of marked RNAs. However, we still lack approaches to directly study how the set of marks for a given RNA molecule shape its fate. In this perspective, we first review current leading approaches in the field. Then, we propose an experimental and computational setup, based on direct RNA sequencing and mathematical modeling, to decipher the functional consequences of RNA modifications on the fate of individual RNA molecules and isoforms.

Highlights

  • More than a 100 RNA modifications have been identified since the 1950s (Boccaletto et al, 2018)

  • Tombo was recently used to identify m6A in yeast with an accuracy of 69% and a recovery of 59%, compared with m6A peaks identified with MeRIP-seq (Liu et al, 2019)

  • Nano-ID was recently developed for detecting the incorporation of the exogenous mark 5eU into nascent RNA (Maier et al, 2019), implementing the analysis of RNA metabolic labeling on the Oxford Nanopore Technologies (ONT) platform

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Summary

Frontiers in Genetics

High-quality methods were developed for the profiling of some of these marks, and approaches to finely study their impact on specific phases of the RNA life-cycle are available, including RNA metabolic labeling. Thanks to these improvements, the most abundant marks, including N6-methyladenosine, are emerging as important determinants of the fate of marked RNAs. we still lack approaches to directly study how the set of marks for a given RNA molecule shape its fate. We still lack approaches to directly study how the set of marks for a given RNA molecule shape its fate In this perspective, we first review current leading approaches in the field.

INTRODUCTION
APPLYING DIRECT RNA SEQUENCING TO QUANTIFY THE DYNAMICS OF MODIFIED RNAs
No Yes No No Yes Yes Yes
Findings
ADDITIONAL REMARKS
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