Roles of the canonical myomiRs miR-1, -133 and -206 in cell development and disease

Figure 2 Alignment of the principal transcripts of the miR-206/miR-133b locus of (A) mouse chromosome 1 and (B) human chromosome 9, compiled from several sources. A: The primary long intergenic non-coding polyadenylated RNA (linc-MD1) of 15 kb is initiated at the upstream distal promoter (DIST) and encompasses both microRNA-206 and -133b genes, however maturation of the pri-linc-MD1 results only in the release of pre-miR-133b which maturates into mir-133b which accumulates in the cell nucleus, as well as the mature 521 bp spliced linc-MD1 RNA which accumulates in the cytoplasm of skeletal muscle cells[38]. The mature linc-MD1 RNA sequence contains binding sites for miR-135 and miR-133 and acts as a complementary “sponge” to regulate their abundance and regulate expression of their target genes including key muscle transcription factors. Accumulation of linc-MD1 RNA and miR-133b are mutually exclusive. The DIST promoter contains E-box sequences recognized by MyoD and is active in differentiating muscle cells when increasing levels of MyoD induce the expression of linc-MD1 or miR-133b. In contrast, the primary transcript of miR-206 initiates at an independent proximal promoter (PROX) which is located intronic to linc-MD1 gene and is already active in undifferentiated proliferating cells. The PROX promoter binds both MyoD and myogenin (ChiP data)[38] and is functional in the presence of myogenin alone, although increased expression activity is also associated with differentiation of muscle cells[11]. The primary expressed transcript for miR-206 is likely coincident with the 5.3 kb random cloned mouse transcript cDNA, GenBank sequence AK132542[40], although the first 13 nt of the pre-mir-206 sequence is absent from that sequence. A second polyadenylated non coding RNA 7H4 was previously identified in rat muscle cells which are specifically associated with nerve synapses[39] and is expressed at rat development stages coincident with the strong expression of MyoD and myogenin[11]. The 5.2 kb long 7H4 ncRNA clone is slightly truncated at the 5’ terminus compared to the AK132542 sequence, and may represent a processed product from which pre-miR-206 has been cleaved[8]. A second 1.6 kb short 7H4 ncRNA transcript, exactly coincident with the 3’ terminal region of the longer transcript, is also abundant in rat muscle[39] and may represent a second processing product; B: The lnc RNA RP11-771D21.2 (Hs.582788) has been identified in RNA seq libraries and aligned with known genomic loci. Information about the regulation of its expression is not available.