Repression of the Hox gene abd-A by ELAV-mediated Transcriptional Interference

Abstract

Intergenic transcription is a common feature of eukaryotic genomes and performs important and diverse cellular functions. Here, we investigate the iab-8 ncRNA from the Drosophila Bithorax Complex and show that this RNA is able to repress the transcription of genes located at its 3’ end by a sequence-independent, transcriptional interference mechanism. Although this RNA is expressed in the early epidermis and CNS, we find that its repressive activity is limited to the CNS, where, in wild-type embryos, it acts on the Hox gene, abd-A, located immediately downstream of it. The CNS specificity is achieved through a 3’ extension of the transcript, mediated by the neuronal-specific, RNA-binding protein, ELAV. Loss of ELAV activity eliminates the 3’ extension and results in the ectopic activation of abd-A. Thus, a tissue-specific change in the length of a ncRNA is used to generate a precise pattern of gene expression in a higher eukaryote.

Dynamic interplay between non-coding enhancer transcription and gene activity in development

“…Transcription of the yeast ADH1 gene is also shown to be suppressed through a similar mechanism during zinc starvation 16 . Similarly, in Drosophila , there are several examples where readthrough non-coding transcription toward the promoter region of nearby genes directly represses their expression 17 , 18 , 52 . In these cases, readthrough non-coding transcription is thought to physically interfere with the assembly of the pre-initiation complex and subsequent recruitment of Pol II to the promoter region.…”

Transcriptional read through interrupts boundary function in Drosophila

“…While previous studies have shown that readthrough transcription can suppress the activity of enhancers and promoters, how this happens is not fully understood [57][58][59]. One idea is that RNA Pol II transiently displaces DNA binding proteins as it passes [60,61].…”

Regulation of the Alternative Neural Transcriptome by ELAV/Hu RNA Binding Proteins

“…Thus, specific mutational experiments are critical to assess phenotypes. Now that we know that ELAV/Hu factors are global regulators of neural APA and splicing, we may expect phenotypic studies of these mutants ( Simionato et al, 2007 ; Rogulja-Ortmann et al, 2014 ; Castro Alvarez et al, 2021 ), or combinations thereof ( Ince-Dunn et al, 2012 ; Wei et al, 2020 ; Lee et al, 2021 ), to lend insight. On the other hand, the extremely broad programs of deregulated splicing and APA isoforms in such mutants also means that it will be challenging to assign specific molecular bases to such mutants, to say nothing of distinguishing direct from indirect effects.…”