Deletion of the sclerotome-enriched lncRNA PEAT augments ribosomal protein expression

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 114; no. 1; pp. 101 - 106
• Main Authors: Stafford, David A., Dichmann, Darwin S., Chang, Jessica K., Harland, Richard M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 03-01-2017
• Subjects: Animals; Biological Sciences; Bone Morphogenetic Proteins - biosynthesis; CRISPR-Cas Systems - genetics; Embryonic Development - genetics; Embryos; Gene expression; Gene Expression Regulation, Developmental - genetics; Mesoderm - embryology; Mice; Mice, Inbred C57BL; Mice, Knockout; Paired Box Transcription Factors - biosynthesis; Paired Box Transcription Factors - genetics; Protein expression; Ribonucleic acid; Ribosomal Proteins - biosynthesis; Ribosomal Proteins - genetics; RNA; RNA, Long Noncoding - genetics; RNA, Ribosomal - biosynthesis; Rodents; Sequence Deletion - genetics; ribosomal proteins; long-noncoding RNA; CRISPR/Cas9; sclerotome; BMP pathway
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1612069113

To define a complete catalog of the genes that are activated during mouse sclerotome formation, we sequenced RNA from embryonic mouse tissue directed to form sclerotome in culture. In addition to well-known early markers of sclerotome, such as Pax1, Pax9, and the Bapx2/Nkx3-2 homolog Nkx3-1, the long-noncoding RNA PEAT (Pax1 enhancer antisense transcript) was induced in sclerotome-directed samples. Strikingly, PEAT is located just upstream of the Pax1 gene. Using CRISPR/Cas9, we generated a mouse line bearing a complete deletion of the PEAT-transcribed unit. RNA-seq on PEAT mutant embryos showed that loss of PEAT modestly increases bone morphogenetic protein target gene expression and also elevates the expression of a large subset of ribosomal protein mRNAs.