Ribosomal protein L24 modulates mammalian microRNA processing and transfer RNA fragment production

Tzur, Y.; Dubnov, S.; Madrer, N.; Bar, A.; Nadorp, B.; Mishra, N.; Heppenstall, P. A.; Bennett, E. R.; Greenberg, D. S.; Winek, K.; Soreq, H.

doi:10.1101/2023.05.03.539194

bioRxiv · 10.1101/2023.05.03.539194

Ribosomal protein L24 modulates mammalian microRNA processing and transfer RNA fragment production

Tzur, Y.·Dubnov, S.·Madrer, N.·Bar, A.·Nadorp, B.·Mishra, N.·Heppenstall, P. A.·Bennett, E. R.·Greenberg, D. S.·Winek, K.·Soreq, H.

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Abstract

The evolutionary mechanism(s) underlying the expression of novel microRNAs (miRs) are still elusive. To explore this issue, we studied the expression of intronic primate-specific hsa-miR-608, located in the Semaphorin 4G (SEMA4G) gene. Engineered humanized mice carrying human miR-608 flanked by 250 bp in the murine Sema4g gene expressed miR-608 in several tissues. Moreover, miR-608 flanked by shortened fragments of its human genome region elevated miR-608 levels by 100-fold in murine and human-originated cells, identifying the 150 nucleotides 5 to pre-miR-608 as an active promoter. Surprisingly, pulldown of this 5 sequence revealed tight interaction with ribosomal protein L24 (RPL24), which inhibited miR-608 expression. Furthermore, RPL24 depletion altered the levels of 22 miRs, and we discovered that direct interaction of RPL24 with DDX5, a component of the large microprocessor complex, inhibits pri-miR processing. Moreover, RPL24 depletion resulted in Angiogenin (ANG)-mediated production of 5-half tRFs in human cells, and altered plant tRF profiles. Expanding previous reports that RPL24 regulates miR processing in Arabidopsis thaliana, we implicate RPL24 in an evolutionarily-conserved regulation of miR processing and tRF production. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/539194v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@4f2058org.highwire.dtl.DTLVardef@d4a2cdorg.highwire.dtl.DTLVardef@c7786org.highwire.dtl.DTLVardef@7b1608_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Tzur, Y., Dubnov, S., Madrer, N., Bar, A., Nadorp, B., Mishra, N., Heppenstall, P. A., Bennett, E. R., Greenberg, D. S., Winek, K., Soreq, H.. 2023-05-03. Ribosomal protein L24 modulates mammalian microRNA processing and transfer RNA fragment production. https://doi.org/10.1101/2023.05.03.539194

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