DROSHA
Ribonuclease 3 (EC 3.1.26.3) (Protein Drosha) (Ribonuclease III) (RNase III) (p241) [RN3] [RNASE3L] [RNASEN]
Publications[править]
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 (PBMCs) 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 mRNAs. The m6A-modified transcripts tend to be more highly expressed than nonmodified ones. Among the many methylated mRNAs, those of DROSHA and AGO2 were heavily methylated in young PBMCs which coincided with a decreased steady-state level of AGO2 mRNA in the old PBMC cohort. Similarly, downregulation of AGO2 in proliferating human diploid fibroblasts (HDFs) also correlated with a decrease in AGO2 mRNA modifications and steady-state levels. In addition, the overexpression of RNA methyltransferases stabilized AGO2 mRNA but not DROSHA and DICER1 mRNA in HDFs. Moreover, the abundance of miRNAs also changed in the young and old PBMCs which are possibly due to a correlation with AGO2 expression as observed in AGO2-depleted HDFs. Taken together, we uncovered the role of mRNA methylation on the abundance of AGO2 mRNA resulting in the repression of miRNA expression during the process of human aging.
MeSH Terms
- Adult
- Aging
- Argonaute Proteins
- Cells, Cultured
- Down-Regulation
- Gene Expression
- Humans
- Male
- Methylation
- Methyltransferases
- Middle Aged
- RNA
- RNA Stability
Keywords
- aging
- m6A RNA methylation
- post transcriptional gene regulation
Centenarians but not octogenarians up regulate the expression of miRNAs, as we previously reported. We have looked into miRNA biogenesis. We show that RNA POL II, DROSHA, EXPORTIN 5 and DICER, are up-regulated in centenarians compared with octogenarians. Furthermore, factors involved in the control of these miRNAs biogenesis genes are also up-regulated in centenarians. Therefore, the up-regulation of miRNA expression in centenarians can be explained in part because miRNA biogenesis pathway is depressed in octogenarians (ordinary aging) while it is maintained in centenarians (extraordinary aging).
MeSH Terms
- Age Factors
- Aged, 80 and over
- Aging
- DEAD-box RNA Helicases
- Humans
- Karyopherins
- MicroRNAs
- RNA Polymerase II
- Ribonuclease III
- Transcriptome
- Up-Regulation
Keywords
- DICER
- DROSHA
- EXPORTIN 5
- Health span
- Longevity
- RNA POL II