Multifaceted roles of YEATS domain-containing proteins and novel links to neurological diseases

Cell Mol Life Sci. 2022 Mar 12;79(3):183. doi: 10.1007/s00018-022-04218-0.

Abstract

The so-called Yaf9, ENL, AF9, Taf14, and Sas5 (YEATS) domain-containing proteins, hereafter referred to as YD proteins, take control over the transcription by multiple steps of regulation either involving epigenetic remodelling of chromatin or guiding the processivity of RNA polymerase II to facilitate elongation-coupled mRNA 3' processing. Interestingly, an increasing amount of evidence suggest a wider repertoire of YD protein's functions spanning from non-coding RNA regulation, RNA-binding proteins networking, post-translational regulation of a few signalling transduction proteins and the spindle pole formation. However, such a large set of non-canonical roles is still poorly characterized. Notably, four paralogous of human YEATS domain family members, namely eleven-nineteen-leukaemia (ENL), ALL1-fused gene from chromosome 9 protein (AF9), YEATS2 and glioma amplified sequence 41 (GAS41), have a strong link to cancer yet new findings also highlight a potential novel role in neurological diseases. Here, in an attempt to more comprehensively understand the complexity of four YD proteins and to gain more insight into the novel functions they may accomplish in the neurons, we summarized the YD protein's networks, systematically searched and reviewed the YD genetic variants associated with neurodevelopmental disorders and finally interrogated the model organism Drosophila melanogaster.

Keywords: Drosophila melanogaster; Epigenetic regulation; Neurological diseases; YEATS domain.

Publication types

  • Review

MeSH terms

  • Animals
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Epigenesis, Genetic
  • Evolution, Molecular
  • Humans
  • Nervous System Diseases / metabolism
  • Nervous System Diseases / pathology*
  • Protein Domains
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Elongation Factors / chemistry
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism*

Substances

  • Chromosomal Proteins, Non-Histone
  • Drosophila Proteins
  • ELL protein, human
  • Transcription Factors
  • Transcriptional Elongation Factors
  • YEATS2 protein, human
  • YEATS4 protein, human