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

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

m⁶A RNA modification / YTHDF2 / RNA metabolism / hematopoiesis / immune regulation / tumor immunity

RIGHTS & PERMISSIONS

The Author(s) 2026. This article is published with open access at link.springer.com and journal.hep.com.cn

Just Accepted

This article has successfully passed peer review and final editorial review, and will soon enter typesetting, proofreading and other publishing processes. The currently displayed version is the accepted final manuscript. The officially published version will be updated with format, DOI and citation information upon launch. We recommend that you pay attention to subsequent journal notifications and preferentially cite the officially published version. Thank you for your support and cooperation.