Characterization of epitranscriptome reader proteins experimentally and in silico: Current knowledge and future perspectives beyond the YTH domain

Miller, Lucas G.; Demny, Madeline; Tamamis, Phanourios; Contreras, Lydia M.

doi:10.1016/j.csbj.2023.06.018

Cited by 4 publications

(1 citation statement)

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“…Additionally, in order to claim that YTHDF proteins show different patterns of binding in the transcriptome, it will also be very important to establish a mechanism for how this can occur. Based on current in vitro binding studies, the YTHDF proteins appear to bind m 6 A regardless of the sequence context ( Miller et al 2023 ). Molecular dynamics simulations using structures of the YTHDF YTH domains also suggest that the YTH domains should have essentially identical binding properties ( Li et al 2020 ).…”

Section: How Can Ythdf1-unique or Ythdf2-unique Sites Be Demonstrated?mentioning

confidence: 99%

Understanding the redundant functions of the m⁶A-binding YTHDF proteins

Zaccara,

Jaffrey

2024

RNA

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N6-methyladenosine (m6A) is the most prevalent modified nucleotide in mRNA and it has important functions in mRNA regulation. However, our understanding of the specific functions of m6A along with its cytosolic readers, the YTHDF proteins, has changed substantially in recent years. The original view was that different m6A sites within an mRNA could have different functions depending on which YTHDF paralog was bound to it, with bound YTHDF1 inducing translation while bound YTHDF2 inducing mRNA degradation. More recent data has called much of this into question, showing that all m6A sites bind all YTHDF proteins with equal ability, with a single primary function of all three YTHDF proteins to mediate mRNA degradation. Here we describe the diverse technical concerns that led to the original model being questioned, the newer data that overturned this model and led to the new understanding of m6A and YTHDF function, and how any remaining questions about the functions of the YTHDF proteins can be readily resolved.

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Section: How Can Ythdf1-unique or Ythdf2-unique Sites Be Demonstrated?mentioning

confidence: 99%