Temasek Life Sciences Laboratory, 1 Research Link National University of Singapore, Singapore 117604, Singapore; Department of Biological Sciences, National University of Singapore, 14 Science Drive Singapore 117543, Singapore.
Temasek Life Sciences Laboratory, 1 Research Link National University of Singapore, Singapore 117604, Singapore.
Cell Rep. 2024 May 28;43(5):114228. doi: 10.1016/j.celrep.2024.114228. Epub 2024 May 11.
Inter-regulation between related genes, such as ribosomal protein (RP) paralogs, has been observed to be important for genetic compensation and paralog-specific functions. However, how paralogs communicate to modulate their expression levels is unknown. Here, we report a circular RNA involved in the inter-regulation between RP paralogs RpL22 and RpL22-like during Drosophila spermatogenesis. Both paralogs are mutually regulated by the circular stable intronic sequence RNA (sisRNA) circRpL22(NE,3S) produced from the RpL22 locus. RpL22 represses itself and RpL22-like. Interestingly, circRpL22 binds to RpL22 to repress RpL22-like, but not RpL22, suggesting that circRpL22 modulates RpL22's function. circRpL22 is in turn controlled by RpL22-like, which regulates RpL22 binding to circRpL22 to indirectly modulate RpL22. This circRpL22-centric inter-regulatory circuit enables the loss of RpL22-like to be genetically compensated by RpL22 upregulation to ensure robust male germline development. Thus, our study identifies sisRNA as a possible mechanism of genetic crosstalk between paralogous genes.
相关基因（如核糖体蛋白 [RP] 同源物）之间的相互调控对于遗传补偿和同源物特异性功能很重要。然而，同源物如何相互交流以调节其表达水平尚不清楚。在这里，我们报道了一个与果蝇精子发生过程中 RP 同源物 RpL22 和 RpL22-like 之间的调控有关的环状 RNA。这两个同源物相互受到来自 RpL22 基因座的环状稳定内含子序列 RNA（sisRNA）circRpL22（NE，3S）的调节。RpL22 抑制自身和 RpL22-like。有趣的是，circRpL22 与 RpL22 结合以抑制 RpL22-like，但不抑制 RpL22，表明 circRpL22 调节 RpL22 的功能。circRpL22 反过来又受到 RpL22-like 的控制，后者调节 RpL22 与 circRpL22 的结合，从而间接调节 RpL22。这种以 circRpL22 为中心的相互调控电路使 RpL22-like 的缺失能够通过 RpL22 的上调得到遗传补偿，从而确保雄性生殖细胞系的稳健发育。因此，我们的研究确定 sisRNA 是同源基因之间遗传串扰的一种可能机制。
