Basis of gene-specific transcription regulation by the Integrator complex.

The Integrator complex attenuates gene expression via the premature termination of RNA polymerase II (RNAP2) at promoter-proximal pausing sites. It is required for stimulus response, cell differentiation, and neurodevelopment, but how gene-specific and adaptive regulation by Integrator is achieved remains unclear. Here, we identify two sites on human Integrator subunits 13/14 that serve as binding hubs for sequence-specific transcription factors (TFs) and other transcription effector complexes.

Global and precise identification of functional miRNA targets in mESCs by integrative analysis.

MicroRNA (miRNA) loaded Argonaute (AGO) complexes regulate gene expression via direct base pairing with their mRNA targets. Previous works suggest that up to 60% of mammalian transcripts might be subject to miRNA-mediated regulation, but it remains largely unknown which fraction of these interactions are functional in a specific cellular context. Here, we integrate transcriptome data from a set of miRNA-depleted mouse embryonic stem cell (mESC) lines with published miRNA interaction predictions and AGO-binding profiles.

Author Correction: Genotypic characterization of multiple drug resistant Escherichia coli isolates from a pediatric cancer hospital in Egypt.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genotypic characterization of multiple drug resistant Escherichia coli isolates from a pediatric cancer hospital in Egypt.

Infection with multiple drug resistant (MDR) Escherichia coli poses a life threat to immunocompromised pediatric cancer patients. Our aim is to genotypically characterize the plasmids harbored in MDR E. coli isolates recovered from bacteremic patients of Children's Cancer Hospital in Egypt 57357 (CCHE 57357).

Bilateral acute depigmentation of the iris in two siblings simultaneously.

Purpose: To report the first simultaneous onset of bilateral acute depigmentation of the iris (BADI) in two siblings.

Observations: Two sisters presented with bilateral ocular pain, redness and light sensitivity. Examination revealed bilateral circulating pigment in the anterior chamber with pigment dusting on backs of the corneas, patchy iris depigmentation and heavy pigment deposition in the angle.

The Conserved Intron Binding Protein EMB-4 Plays Differential Roles in Germline Small RNA Pathways of C. elegans.

Proper regulation of the germline transcriptome is essential for fertility. In C. elegans, germline homeostasis hinges on a complex repertoire of both silencing and activating small RNA pathways, along with RNA processing.

The Helicase Aquarius/EMB-4 Is Required to Overcome Intronic Barriers to Allow Nuclear RNAi Pathways to Heritably Silence Transcription.

Small RNAs play a crucial role in genome defense against transposable elements and guide Argonaute proteins to nascent RNA transcripts to induce co-transcriptional gene silencing. However, the molecular basis of this process remains unknown. Here, we identify the conserved RNA helicase Aquarius/EMB-4 as a direct and essential link between small RNA pathways and the transcriptional machinery in Caenorhabditis elegans.

Examining the intersection between splicing, nuclear export and small RNA pathways.

Background: Nuclear Argonaute/small RNA pathways in a variety of eukaryotic species are generally known to regulate gene expression via chromatin modulation and transcription attenuation in a process known as transcriptional gene silencing (TGS). However, recent data, including genetic screens, phylogenetic profiling, and molecular mechanistic studies, also point to a novel and emerging intersection between the splicing and nuclear export machinery with nuclear Argonaute/small RNA pathways in many organisms.

Scope Of Review: In this review, we summarize the field's current understanding regarding the relationship between splicing, export and small RNA pathways, and consider the biological implications for coordinated regulation of transcripts by these pathways.