Active genic machinery for epigenetic RNA modifications in bees

Abstract

Epitranscriptomics is an emerging field of investigation dedicated to the study of post‐transcriptional RNA modifications. RNA methylations regulate RNA metabolism and processing, including changes in response to environmental cues. Although RNA modifications are conserved from bacteria to eukaryotes, there is little evidence of an epitranscriptomic pathway in insects. Here we identified genes related to RNA m6A (N6‐methyladenine) and m5C (5‐methylcytosine) methylation machinery in seven bee genomes (Apis mellifera, Melipona quadrifasciata, Frieseomelitta varia, Eufriesea mexicana, Bombus terrestris, Megachile rotundata and Dufourea novaeangliae). In A. mellifera, we validated the expression of methyltransferase genes and found that the global levels of m6A and m5C measured in the fat body and brain of adult workers differ significantly. Also, m6A levels were differed significantly mainly between the fourth larval instar of queens and workers. Moreover, we found a conserved m5C site in the honeybee 28S rRNA. Taken together, we confirm the existence of epitranscriptomic machinery acting in bees and open avenues for future investigations on RNA epigenetics in a wide spectrum of hymenopteran species.

Transcriptional expression of m6A and m5C RNA methyltransferase genes in the brain and fat body of honey bee adult workers

“… Bataglia et al (2021) reported that global levels of m 6 A and m 5 C methylation quantified in the total RNA from brain and fat body samples increases in age progression. In this study we observed an increase in the expression of RNA methyltransferases in brain which is in accordance with the overall increase in global m 6 A and m 5 C methylation levels ( Bataglia et al, 2021 ).…”

“… Bataglia et al (2021) reported that global levels of m 6 A and m 5 C methylation quantified in the total RNA from brain and fat body samples increases in age progression. In this study we observed an increase in the expression of RNA methyltransferases in brain which is in accordance with the overall increase in global m 6 A and m 5 C methylation levels ( Bataglia et al, 2021 ). However, in the fat body, although the higher expression of RNA methyltransferases is found in younger bees, the global m 6 A and m 5 C methylation levels are lower in young bees when compared with older bees.…”

“…In Bombyx mori , m 6 A was reported to control gene expression and cell cycle progression ( Li et al, 2019 ). In honey bees, two studies revealed RNA modifications acting in caste differentiation ( Bataglia et al, 2021 ; Wang et al, 2021 ). Our group recently identified the orthologs of RNA methyltransferase genes in the A. mellifera genome, being METTL3 (methyltransferase like 3) and METTL14 (methyltransferase like 14) for m 6 A methylation, and DNMT2 (DNA methyltransferase 2) and the NSUN (NOP2/Sun RNA methyltransferase member) family encoding genes (NOP2, NSUN2, NSUN4, NSUN5, and NSUN7) for m 5 C methylation ( Bataglia et al, 2021 ).…”

Extent and complexity of RNA processing in honey bee queen and worker caste development

“…Moreover, epigeneic modifications such as DNA methylation, microRNA, and alternative chromatin states have been shown to be involved in the regulation of honeybee queen-worker dimorphism ( Foret et al., 2012 ; Ashby et al., 2016 ; Guo et al., 2016 ; Wojciechowski et al., 2018 ). The latest evidence showed that m6A methylation on RNA also participates in the genomic regulation leading to queen-worker dimorphism ( Bataglia et al., 2021 ; Wang et al., 2021 ).…”

Dual isoform sequencing reveals complex transcriptomic and epitranscriptomic landscapes of a prototype baculovirus

“…Early works leading to the discovery of the mRNA Cap structure have detected a low level of internal 5-methylcitosine (5-mC) in the mammalian and insect cells 19 , 20 . Later studies have also detected the presence of methylated nucleotides in viral RNAs 21 , 22 .…”