nuclear accumulation of an uncapped rna produced by drosha cleavage of a transcript encoding mir-10b and hoxd4核无上限的rna的积累所产生的记录编码mir-10b和hoxd4 drosha乳沟.pdfVIP

Nuclear Accumulation of an Uncapped RNA Produced by Drosha Cleavage of a Transcript Encoding miR-10b and HOXD4 1 2 1 1 1 2 Sze Lynn Calista Phua , V. Sivakamasundari , Yu Shao , Xiaohan Cai , Li-Feng Zhang , Thomas Lufkin , Mark Featherstone1* 1 School of Biological Sciences, Nanyang Technological University, Singapore, 2 Genome Institute of Singapore, Singapore Abstract Patterning of the animal embryo’s antero-posterior (AP) axis is dependent on spatially and temporally regulated Hox gene expression. The murine Hoxd4 gene has been proposed to harbour two promoters, an upstream promoter P2, and a downstream promoter P1, that lie 5.2 and 1.1 kilobase pairs (kb) upstream of the coding region respectively. The evolutionarily conserved microRNA-10b (miR-10b) gene lies in the Hoxd4 genomic locus in the intron separating the non- coding exons 4 and 5 of the P2 transcript and directly adjacent to the proposed P1 promoter. Hoxd4 transcription is regulated by a 39 neural enhancer that harbours a retinoic acid response element (RARE). Here, we show that the expression profiles of Hoxd4 and miR-10b transcripts during neural differentiation of mouse embryonal carcinoma (EC) P19 cells are co- ordinately regulated, suggesting that both Hoxd4 and miR-10b expression is governed by the neural enhancer. Our observation that P1 transcripts are uncapped, together with the mapping of their 59 ends, strongly suggests that they are generated by Drosha cleavage of P2 transcripts rather than by transcriptional initiation. This is supported by the colocalization of P1 and P2 transcripts to the same posterior expression domain in