Juvenile hormone-regulated alternative splicing of thetaimangene primes the ecdysteroid response in adult mosquitoes

Abstract

Juvenile hormone (JH) regulates many aspects of insect development and reproduction. In some processes, JH plays a critical role in defining the action of the steroid hormone 20-hydroxyecdysone (20E). In mosquitoes, JH prepares newly emerged female adults to become competent to synthesize vitellogenin in response to 20E after blood ingestion. The molecular basis of this competence is still not well understood. Here, we report that JH regulates pre-mRNA splicing of the gene, which encodes a key transcriptional regulator required for both JH- and 20E-controlled gene expression. JH stimulated the production of the Taiman isoforms A/B, while reducing the levels of the isoforms C/D, in the fat body after adult eclosion. The appearance of the A/B isoforms in maturing mosquitoes was accompanied by acquisition of the competence to respond to 20E. Depletion of the A/B isoforms, by inhibiting the alternative splicing or by isoform-specific RNA interference, considerably diminished the 20E-induced gene expression after a blood meal and substantially impaired oocyte development. In accordance with this observation, further studies indicated that in the presence of 20E, the Taiman A/B isoforms showed much stronger interactions with the 20E receptor complex than the Taiman C/D isoforms. In contrast, all four isoforms displayed similar capabilities of forming active JH receptor complexes with the methoprene-tolerant protein (Met). This study suggested that JH confers the competence to newly emerged female mosquitoes by regulating mRNA splicing to generate the Taiman isoforms that are essential for the vitellogenic 20E response.

Juvenile hormone affects the splicing of Culex quinquefasciatus early trypsin messenger RNA

“…We report for the first time, that JH III is important in the splicing of the early trypsin pre‐mRNA (Figure ) in Cx. quinquefasciatus and Liu et al () reported that in female Ae. aegypti JH controls the alternative splicing of the taiman gene.…”

“…However, no attempt to find out whether JH has a role in the transcription or translation of these enzymes was investigated. A recent report by Liu, Fu, and Zhu (), on the other hand, showed that in female Ae. aegypti JH regulates the alternative splicing of the taiman gene allowing a response to ecdysteroid stimulation during vitellogenesis.…”

Juvenile hormone acts through FoxO to promote Cdc2 and Orc5 transcription for polyploidy-dependent vitellogenesis

“…In addition, JH acts via the RTK-PLC-IP3-CaMKII signaling cascade to trigger the phosphorylation of Met for enhanced transcriptional activity in the mosquito Aedes aegypti (Liu et al, 2015;Ojani et al, 2016). Moreover, JH, through the RTK-PI3K-Akt signaling pathway, stimulates the phosphorylation of serine/arginine-rich (pre-mRNA) splicing factor (SRSF) to induce the alternative splicing of Tai (Liu et al, 2018). The produced Tai-A and Tai-B isoforms potentiate the transcriptional activity of 20Ereceptor in the fat body of adult female mosquitoes essential for blood meal-induced vitellogenesis and egg production (Liu et al, 2018).…”

“…Moreover, JH, through the RTK-PI3K-Akt signaling pathway, stimulates the phosphorylation of serine/arginine-rich (pre-mRNA) splicing factor (SRSF) to induce the alternative splicing of Tai (Liu et al, 2018). The produced Tai-A and Tai-B isoforms potentiate the transcriptional activity of 20Ereceptor in the fat body of adult female mosquitoes essential for blood meal-induced vitellogenesis and egg production (Liu et al, 2018). In the cotton bollworm Helicoverpa armigera, JH acts on the phosphorylation of the pupal specifier, Broad-complex (Br-C) Development • Accepted manuscript to repress 20E-initated metamorphosis via the GPCR-PLC-PKC pathway (Cai et al, 2014).…”

Transcriptome Analysis Reveals Candidate Genes During the Prepupal-pupal Transition in the Oriental Armyworm, Mythimna separata (Walker) (Lepidoptera: Noctuidae)

“…However, the effects of the two hormones are opposite; JH maintains insect growth in larvae, whereas 20E induces metamorphosis at the mature larvae [21,22]. Regulation of metamorphosis by hormones has been studied in many insects, including Bombyx mori [23], Aedes aegypti [24], Laodelphax striatellus [25] and so on. These results indicate that JH and 20E co-mediate the prepupal-pupal metamorphosis process of insects by changing the expression patterns of CPs in various tissues and different developmental stages.…”