Spatiotemporal expression of long noncoding RNA Moshe modulates heart cell lineage commitment

• Published in: RNA biology Vol. 18; no. S2; pp. 640 - 654
• Main Authors: Kim, Na-Jung, Lee, Kang-Hoon, Son, YeonSung, Nam, A-Reum, Moon, Eun-Hye, Pyun, Jung-Hoon, Park, Jinyoung, Kang, Jong-Sun, Lee, Young Jae, Cho, Je-Yoel
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 12.11.2021
• Subjects: Animals; atrial septal defect; Cell Differentiation - genetics; Cell Line; Cell Lineage - genetics; Enhancer Elements, Genetic; Gata6 antisense transcript; GATA6 Transcription Factor - genetics; Gene Expression Profiling; Gene Expression Regulation, Developmental; Gene Knockdown Techniques; heart development; Humans; Long non-coding RNA; Mesoderm - embryology; Mesoderm - metabolism; Mice; Myoblasts, Cardiac - cytology; Myoblasts, Cardiac - metabolism; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Organogenesis - genetics; Promoter Regions, Genetic; Research Paper; RNA Interference; RNA, Antisense; RNA, Long Noncoding - genetics; second heart field; heart development; Gata6 antisense transcript; atrial septal defect; Long non-coding RNA; second heart field
• ISSN: 1547-6286; 1555-8584
• DOI: 10.1080/15476286.2021.1976549

The roles of long non-coding RNA (LncRNA) have been highlighted in various development processes including congenital heart defects (CHD). Here, we characterized the molecular function of LncRNA, Moshe (1010001N08ik-203), one of the Gata6 antisense transcripts located upstream of Gata6, which is involved in both heart development and the most common type of congenital heart defect, atrial septal defect (ASD). During mouse embryonic development, Moshe was first detected during the cardiac mesoderm stage (E8.5 to E9.5) where Gata6 is expressed and continues to increase at the atrioventricular septum (E12.5), which is involved in ASD. Functionally, the knock-down of Moshe during cardiogenesis caused significant repression of Nkx2.5 in cardiac progenitor stages and resulted in the increase in major SHF lineage genes, such as cardiac transcriptional factors (Isl1, Hand2, Tbx2), endothelial-specific genes (Cd31, Flk1, Tie1, vWF), a smooth muscle actin (a-Sma) and sinoatrial node-specific genes (Shox2, Tbx18). Chromatin Isolation by RNA Purification showed Moshe activates Nkx2.5 gene expression via direct binding to its promoter region. Of note, Moshe was conserved across species, including human, pig and mouse. Altogether, this study suggests that Moshe is a heart-enriched lncRNA that controls a sophisticated network of cardiogenesis by repressing genes in SHF via Nkx2.5 during cardiac development and may play an important role in ASD.