Identification of mammalian microRNA host genes and transcription units

Abstract

To derive a global perspective on the transcription of microRNAs (miRNAs) in mammals, we annotated the genomic position and context of this class of noncoding RNAs (ncRNAs) in the human and mouse genomes. Of the 232 known mammalian miRNAs, we found that 161 overlap with 123 defined transcription units (TUs). We identified miRNAs within introns of 90 protein-coding genes with a broad spectrum of molecular functions, and in both introns and exons of 66 mRNA-like noncoding RNAs (mlncRNAs). In addition, novel families of miRNAs based on host gene identity were identified. The transcription patterns of all miRNA host genes were curated from a variety of sources illustrating spatial, temporal, and physiological regulation of miRNA expression. These findings strongly suggest that miRNAs are transcribed in parallel with their host transcripts, and that the two different transcription classes of miRNAs ('exonic' and 'intronic') identified here may require slightly different mechanisms of biogenesis.

Figure 1

Genomic organization of the mammalian miR-100, let-7a-2, miR-125b-1 locus and sequence alignment of human and mouse miR-125b-1 host transcripts. (A) Identified transcripts are shown with exons represented as vertical lines and labeled above in numerical order. Dotted lines denote splicing of transcripts. Positions of miRNA precursors are denoted with a triangle. Exons are not to scale. Human/Mouse Transcript 1 corresponds to ENSESTT00000036713 and ENSMUSESTT00000030830, respectively. Transcript 2 corresponds to human ENSESTT00000036715 and mouse 2610203C20Rik transcripts. (B) A DNA sequence alignment for Transcript 2 is shown. Identical bases are denoted in black. Consensus polyadenylation sites are boxed in. Note that nucleotides 597-955 of the human Transcript 2 are not shown.

Figure 2

Genomic organization of the mammalian miR-22 locus and sequence alignment of human and mouse miR-22 host transcripts. (A) Exons are shown as white rectangles and labeled above. The human/mouse miR-22 host transcript corresponds to ENSESTT00000065902 and 2210403K04Rik, respectively. (B) DNA sequence alignments of the miR-22 human/mouse host transcripts are shown. Identical bases are black. The mature miR-22 sequence is highlighted in gray. The conserved splice site junction between exons 1 and 2 is also highlighted in gray. Note that nucleotides 688-1658 of the mouse transcript are not shown.