CAS Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Chinese Academy of Sciences, Institute of Oceanology, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
CAS Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Chinese Academy of Sciences, Institute of Oceanology, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China; University of Chinese Academy of Sciences, Beijing, China.
Comp Biochem Physiol B Biochem Mol Biol. 2021 Jun-Jul;254:110578. doi: 10.1016/j.cbpb.2021.110578. Epub 2021 Feb 18.
MiR-150 is a microRNA (miRNA) present in a number of teleost species, but its target and regulation mechanism are unknown. Similarly, lysosome membrane protein 2-like (LMP2L) is a gene identified in fish but with unknown function. In this study, we examined the regulation mechanism and function of flounder miR-150 (named pol-miR-150) and its target gene LMP2L (named PoLMP2L) in association with bacterial and viral infection. We found that pol-miR-150 expression was not only modulated by the bacterial pathogen Streptococcus iniae but also by the viral pathogen megalocytivirus. Pol-miR-150 targeted PoLMP2L by binding to the 3'-untranslated region (3'-UTR) of PoLMP2L and inhibited PoLMP2L expression in vitro and in vivo. PoLMP2L is a member of the CD36 superfamily of scavenger receptors and homologous to but phylogenetically distinct from lysosomal integral membrane protein type 2 (LIMP2). PoLMP2L was localized mainly in the lysosomes and expressed in multiple organs of flounder. In vivo knockdown and overexpression of PoLMP2L enhanced and suppressed, respectively, S. iniae dissemination in flounder tissues, whereas in vivo knockdown and overexpression of pol-miR-150 produced the opposite effects on S. iniae dissemination. In addition, pol-miR-150 knockdown also significantly inhibited the replication of megalocytivirus. The results of this study revealed the regulation mechanism and immune functions of fish miR-150 and LMP2L, and indicated that LMP2L and miR-150 play an important role in the antimicrobial immunity of fish.
miR-150 是一种存在于许多硬骨鱼类中的 microRNA (miRNA)，但其靶基因和调控机制尚不清楚。同样，溶酶体膜蛋白 2 样（LMP2L）是在鱼类中鉴定的一个基因，但功能未知。在这项研究中，我们研究了牙鲆 miR-150（命名为 pol-miR-150）及其靶基因 LMP2L（命名为 PoLMP2L）在与细菌和病毒感染相关的调控机制和功能。我们发现，pol-miR-150 的表达不仅受细菌病原体链球菌的调节，还受病毒病原体虹彩病毒的调节。pol-miR-150 通过与 PoLMP2L 的 3'-非翻译区（3'-UTR）结合来靶向 PoLMP2L，并在体外和体内抑制 PoLMP2L 的表达。PoLMP2L 是 CD36 家族清道夫受体的成员，与溶酶体整合膜蛋白 2 型（LIMP2）同源，但在系统发育上不同。PoLMP2L 主要定位于溶酶体中，并在牙鲆的多个器官中表达。体内敲低和过表达 PoLMP2L 分别增强和抑制了链球菌在牙鲆组织中的传播，而体内敲低和过表达 pol-miR-150 对链球菌的传播则产生了相反的影响。此外，pol-miR-150 的敲低也显著抑制了虹彩病毒的复制。本研究结果揭示了鱼类 miR-150 和 LMP2L 的调控机制和免疫功能，表明 LMP2L 和 miR-150 在鱼类的抗菌免疫中发挥重要作用。
