Open AccessProfiling of m6A RNA modifications identified an age‐associated regulation of AGO 2 mRNA stability
Author(s) -
Min KyungWon,
Zealy Richard W.,
Davila Sylvia,
Fomin Mikhail,
Cummings James C.,
Makowsky Daniel,
Mcdowell Catherine H.,
Thigpen Haley,
Hafner Markus,
Kwon SangHo,
Georgescu Constantin,
Wren Jonathan D.,
Yoon JeHyun
Publication year - 2018
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12753
Subject(s) - drosha , biology , messenger rna , rna , methylation , microbiology and biotechnology , transcription (linguistics) , dicer , microrna , gene expression , rna binding protein , peripheral blood mononuclear cell , rna methylation , methyltransferase , three prime untranslated region , untranslated region , gene , genetics , rna interference , in vitro , linguistics , philosophy
Summary Gene expression is dynamically regulated in a variety of mammalian physiologies. During mammalian aging, there are changes that occur in protein expression that are highly controlled by the regulatory steps in transcription, post‐transcription, and post‐translation. Although there are global profiles of human transcripts during the aging processes available, the mechanism(s) by which transcripts are differentially expressed between young and old cohorts remains unclear. Here, we report on N6‐methyladenosine (m6A) RNA modification profiles of human peripheral blood mononuclear cells ( PBMC s) from young and old cohorts. An m6A RNA profile identified a decrease in overall RNA methylation during the aging process as well as the predominant modification on proteincoding mRNA s. The m6A‐modified transcripts tend to be more highly expressed than nonmodified ones. Among the many methylated mRNA s, those of DROSHA and AGO 2 were heavily methylated in young PBMC s which coincided with a decreased steady‐state level of AGO 2 mRNA in the old PBMC cohort. Similarly, downregulation of AGO 2 in proliferating human diploid fibroblasts ( HDF s) also correlated with a decrease in AGO 2 mRNA modifications and steady‐state levels. In addition, the overexpression of RNA methyltransferases stabilized AGO 2 mRNA but not DROSHA and DICER 1 mRNA in HDF s. Moreover, the abundance of mi RNA s also changed in the young and old PBMC s which are possibly due to a correlation with AGO 2 expression as observed in AGO 2‐depleted HDF s. Taken together, we uncovered the role of mRNA methylation on the abundance of AGO 2 mRNA resulting in the repression of mi RNA expression during the process of human aging.