Noncoding RNAs of the Ultrabithorax Domain of the Drosophila Bithorax Complex

Abstract

RNA transcripts without obvious coding potential are widespread in many creatures, including the fruit fly, Drosophila melanogaster. Several noncoding RNAs have been identified within the Drosophila bithorax complex. These first appear in blastoderm stage embryos, and their expression patterns indicate that they are transcribed only from active domains of the bithorax complex. It has been suggested that these noncoding RNAs have a role in establishing active domains, perhaps by setting the state of Polycomb Response Elements A comprehensive survey across the proximal half of the bithorax complex has now revealed nine distinct noncoding RNA transcripts, including four within the Ultrabithorax transcription unit. At the blastoderm stage, the noncoding transcripts collectively span 75% of the 135 kb surveyed. Recombination-mediated cassette exchange was used to invert the promoter of one of the noncoding RNAs, a 23-kb transcript from the bxd domain of the bithorax complex. The resulting animals fail to make the normal bxd noncoding RNA and show no transcription across the bxd Polycomb Response Element in early embryos. The mutant flies look normal; the regulation of the bxd domain appears unaffected. Thus, the bxd noncoding RNA has no apparent function.

Regulation of Transcription by Long Noncoding RNAs

“…Later, it was suggested that lncRNAs repress Ultrabithorax via transcriptional interference (128). Most recently, genetic inactivation of one such lncRNA resulted in no discernible phenotype (127). Another famous example is pgc , which was first proposed to function as lncRNA (108) but later shown to encode a 71-aa protein responsible for gene function (56).…”

Hox miRNA regulation within the Drosophila Bithorax complex: Patterning behavior

“…The bxd region is transcribed in early embryos and larval/pupal stages to yield polyadenylated transcripts of 1.1–1.3 kb and 0.8 kb. More recently, Bender’s group used embryo in situ hybridizations to provide evidence for 7 additional non-coding transcripts in the Ubx-bxd region, arising from both DNA strands (Pease et al, 2013). …”

“…For example, although a huge amount of embryonic mRNA-seq and total RNA-seq data now exist, for the most part, these were performed from whole embryo samples. Notably, earlier in situ studies detected transient expression of additional putative short iab RNAs in specific domains of the A/P axis other than A8 and A9 during early embryonic development (Bae et al, 2002; Sanchez-Herrero and Akam, 1989) (Pease et al, 2013), whose molecular identities remain undetermined. One can imagine that further sequencing of polyadenylated and rRNA-depleted RNAs from specific axial domains across development, may produce further insights.…”

“…On the other hand, non-coding transcription in the BX-C might interfere with that of downstream of protein-coding gene promoters, as proposed for the effect of bxd transcription on Ubx (Petruk et al, 2006), or iab -8 transcription on abd-A (Gummalla et al, 2012). Given that painstaking genetic efforts to precisely eliminate a major BX-C ncRNA ( bxd ) did not yield substantial regulatory or phenotypic defects (Pease et al, 2013), the possibility remains that many BX-C ncRNAs might represent products of transcriptional noise associated with enhancers. Since miRNAs are typically considered as trans-regulatory species, then, it becomes especially germane to ask whether these BX-C miRNAs indeed have any functional consequence to the regulation or function of the BX-C.…”

Transcription through Polycomb response elements does not induce a switch from repression to activation

“…In particular, Pease et al (16) This transcript is expressed in the same domain as Ubx and might be expected to antagonize bxd PRE-bound PcG protein binding and silencing activity. Pease et al found that eliminating transcription through the bxd PRE caused no defect in Ubx expression or any other aspect of fly development (16). So, at least in this case, transcription through the PRE does not appear to be physiologically relevant to antagonize the silencing capacity of this element.…”