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Lamprey immune protein (LIP) is a key immune regulator. MicroRNAs, well-conserved in the response to immunological stress, remain understudied in lamprey immunity. We generated a lamprey microRNA expression atlas, using deep sequencing, upon<jats:italic>Vibrio anguillarum<\/jats:italic>infection. Using comparative methods, we found that miR-4561 potentially regulates innate immunity via interaction with<jats:italic>lip<\/jats:italic>. We found a sequence in the 3\u2032-UTR region of LIP mRNA complementary to the miR-4561 seed region; miR-4561 expression was negatively correlated with LIP. During<jats:italic>V. anguillarum<\/jats:italic>infection, miR-4561 inhibited LIP expression and bacterial clearance. Notably, LIP expression in supraneural body cells was necessary for the Gram-negative immune response. Additionally, we observed that overexpression of miR-4561 induced apoptosis in embryonic cells, suggesting a role in embryonic development. Collectively, we show lamprey microRNAs may significantly affect gene regulation and provide new insights on LIP-mediated immune regulation.<\/jats:p>","DOI":"10.1038\/s42003-021-02525-z","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T10:02:51Z","timestamp":1629453771000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["MicroRNA expression profile in Lampetra morii upon Vibrio anguillarum infection and miR-4561 characterization targeting lip"],"prefix":"10.1038","volume":"4","author":[{"given":"Lie","family":"Ma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Gou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeyu","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9869-2863","authenticated-orcid":false,"given":"Yue","family":"Pang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"2525_CR1","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1098\/rspb.2010.1641","volume":"278","author":"RS Sansom","year":"2011","unstructured":"Sansom, R. 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