MicroRNA biogenesis is broadly disrupted by inhibition of the splicing factor SF3B1.

In animals, microRNA (miRNA) biogenesis begins with cotranscriptional cleavage of the primary (pri-)miRNA by the Microprocessor complex. Cotranscriptional splicing has been shown to influence Microprocessor cleavage when miRNAs are hosted in introns of protein-coding pri-miRNAs, but the impact of splicing on production of miRNAs hosted in long non-coding (lnc)RNAs is largely unknown. Here, we investigated the role of splicing in the biogenesis of miR-122, an lncRNA-hosted, highly expressed, medically important, liver-specific miRNA.

A Simple Whole-Plasmid PCR Method to Construct High-Diversity Synthetic Phage Display Libraries.

Phage display technology utilises peptide and antibody libraries with very high diversities to select ligands with specific binding properties. The production of such libraries can be labour intensive and technically challenging and whilst there are commercial sources of libraries, the exploitation of the resulting binders is constrained by ownership of the libraries. Here, a peptide library of ~ 1 × 10 variants for display on gene VIII was produced alongside three VHH antibody libraries with similar diversity, where 12mer, 16mer or 21mer CDR3s were introduced into the highly stable cAbBCII10 scaffold displayed on gene III.

BRCA1/MAD2L1 Deficiency Disrupts the Spindle Assembly Checkpoint to Confer Vinorelbine Resistance in Mesothelioma.

Mesothelioma is a universally lethal cancer lacking effective therapy. The spindle poison vinorelbine exhibits clinical activity in the relapsed setting, and in preclinical models requires to initiate apoptosis. However, the mechanisms underlying this regulation and the clinical implications have not been explored.

Eukaryotic translation initiation factor 4AII contributes to microRNA-122 regulation of hepatitis C virus replication.

Hepatitis C virus (HCV) is a positive sense RNA virus that persistently infects human liver, leading to cirrhosis and hepatocellular carcinoma. HCV replication requires the liver-specific microRNA-122 (miR-122). In contrast to canonical miRNA-mediated repression via 3'UTR sites, miR-122 positively regulates HCV replication by a direct interaction with the 5' untranslated region (UTR) of the viral RNA.