Emerging role of RNA modification reader YTHDF2 in hematopoiesis, immunity, and cancer

MedScience. 2026 Feb;20(1):59-77. doi: 10.1007/s11684-026-1203-5. Epub 2026 Apr 1.

Abstract

N6-methyladenosine (m6A) RNA modification has emerged as a pivotal epitranscriptomic mark shaping RNA metabolism and cellular programs. Among the diverse m6A reader proteins, YTHDF2 has garnered significant attention as a key regulator of RNA stability. Recent studies highlight the multifaceted roles of YTHDF2 in orchestrating hematopoietic stem cell self-renewal and differentiation, fine-tuning immune cell development and function, and modulating tumor-immune interactions within the tumor microenvironment. YTHDF2 has also been shown to function as a reader for RNA 5-methylcytosine (m5C) modification. By linking m6A- and/or m5C-dependent RNA dynamics to hemato-immune homeostasis, YTHDF2 functions as a central epitranscriptomic integrator linking intrinsic genetic programs to developmental and environmental cues. Here, we summarize current advances in understanding YTHDF2-mediated RNA regulation across physiological and pathological contexts, discuss its potential as a therapeutic target in immune-related diseases and cancers, and highlight future directions in the field.

Keywords: RNA metabolism; YTHDF2; hematopoiesis; immune regulation; m6A RNA modification; tumor immunity.

Publication types

  • Review

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / metabolism
  • Animals
  • Hematopoiesis* / genetics
  • Humans
  • Immunity* / genetics
  • Neoplasms* / genetics
  • Neoplasms* / immunology
  • Neoplasms* / metabolism
  • RNA* / genetics
  • RNA* / metabolism
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • Tumor Microenvironment / immunology

Substances

  • RNA-Binding Proteins
  • YTHDF2 protein, human
  • RNA
  • N-methyladenosine
  • Adenosine