The Germinal Center Reaction Depends on RNA Methylation and Divergent Functions of Specific Methyl Readers

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2021 Aug 17

PMID 34402854

Citations 20

Authors

Amalie C Grenov

Lihee Moss

Sarit Edelheit

Ross Cordiner

Dominik Schmiedel

Adi Biram

Jacob H Hanna

Torben Heick Jensen

Schraga Schwartz

Ziv Shulman

Affiliations

Soon will be listed here.

Abstract

Long-lasting immunity depends on the generation of protective antibodies through the germinal center (GC) reaction. N6-methyladenosine (m6A) modification of mRNAs by METTL3 activity modulates transcript lifetime primarily through the function of m6A readers; however, the physiological role of this molecular machinery in the GC remains unknown. Here, we show that m6A modifications by METTL3 are required for GC maintenance through the differential functions of m6A readers. Mettl3-deficient GC B cells exhibited reduced cell-cycle progression and decreased expression of proliferation- and oxidative phosphorylation-related genes. The m6A binder, IGF2BP3, was required for stabilization of Myc mRNA and expression of its target genes, whereas the m6A reader, YTHDF2, indirectly regulated the expression of the oxidative phosphorylation gene program. Our findings demonstrate how two independent gene networks that support critical GC functions are modulated by m6A through distinct mRNA binders.

Citing Articles

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