Date Published: May 30, 2019
Publisher: Public Library of Science
Author(s): Li Zhu, Susan E. Liao, Yiwei Ai, Ryuya Fukunaga, Jorge Perez-Fernandez.
RNA methyltransferases post-transcriptionally add methyl groups to RNAs, which can regulate their fates and functions. Human BCDIN3D (Bicoid interacting 3 domain containing RNA methyltransferase) has been reported to specifically methylate the 5′-monophosphates of pre-miR-145 and cytoplasmic tRNAHis. Methylation of the 5′-monophosphate of pre-miR-145 blocks its cleavage by the miRNA generating enzyme Dicer, preventing generation of miR-145. Elevated expression of BCDIN3D has been associated with poor prognosis in breast cancer. However, the biological functions of BCDIN3D and its orthologs remain unknown. Here we studied the biological and molecular functions of CG1239, a Drosophila ortholog of BCDIN3D. We found that ovary-specific knockdown of Drosophila BCDIN3D causes female sterility. High-throughput sequencing revealed that miRNA and mRNA profiles are dysregulated in BCDIN3D knockdown ovaries. Pathway analysis showed that many of the dysregulated genes are involved in metabolic processes, ribonucleoprotein complex regulation, and translational control. Our results reveal BCDIN3D’s biological role in female fertility and its molecular role in defining miRNA and mRNA profiles in ovaries.
The epitranscriptome describes over 200 types of post-transcriptional RNA modifications, which can regulate the fates and functions of RNAs [1–3]. Post-transcriptional modification can occur on bases, riboses, and termini of RNAs. Dysregulation of RNA modification is associated with neurological disorders, cancers, and other diseases in human .
In this study, we show that ovary-specific knockdown of Drosophila BCDIN3D causes female sterility without clear morphological defect in ovaries (Fig 1). High-throughput sequencing studies demonstrated that BCDIN3D plays important roles in defining miRNA and mRNA profiles in ovaries (Figs 2–6).