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PNAS Papers on Inflammatory Bowel Disease Telomeres, Mosquito MicroRNAs, More

Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted this week.

An MD Anderson Cancer Center-led team describes a role for altered telomere function in inflammatory bowel disease-related inflammation. Following from prior intestinal epithelium findings in a mouse model of IBD, the researchers used a fluorescence in situ hybridization assay, RNA sequencing, and other approaches to look at the consequences of telomere dysfunction in intestinal biopsy samples from individuals with older-onset IBD and in organoid models of Crohn's disease or ulcerative colitis. Their results point to inflammatory activation in the presence of telomere dysfunction via enhanced expression of an IBD driver called precursor of interleukin 19 (pro-IL-18), which is part of a pathway with ATM and YAP1. "In organoid models from ulcerative colitis and Crohn's disease patients, pharmacological interventions of telomerase reactivation, suppression of DNA damage signaling, or YAP1 inhibition reduced pro-IL-18 production," the authors report, noting that such data "support a model wherein telomere dysfunction in the intestinal epithelium can initiate the inflammatory process in IBD, pointing to therapeutic interventions for this disease."

University of California, Riverside, researchers report on microRNA regulation in the dengue virus mosquito vector Aedes aegypti, focusing on a mechanism mediated by a mosquito reproduction-related juvenile hormone and the E75 transcription factor isoform E75-RD. The team saw ties between E75-RD and miRNA gene promoter induction using an RNA interference-based transcription factor screen, exploring those findings further with RNA sequencing, small RNA sequencing, computational analyses, and other approaches. "Our study focused on the control of miRNAs due to their importance as regulators of gene expression in reproduction in the disease vector Ae. aegypti," the investigators say, adding that "the present work not only highlights a previously unidentified role for E75-RD as a factor within the [juvenile hormone] hierarchical network but also demonstrates E75-RD as a critical regulator of miRNA expression in the mosquito."

A team from Fudan University Shanghai Cancer Center and elsewhere looks at long non-coding RNA ties to p53 tumor suppressor inactivation. With array-based expression profiling and RMRP-targeted qPCR on 79 colorectal cancer (CRC) samples and more than a dozen matched normal samples, the investigators found that a lncRNA known as the "RNA component of the mitochondrial RNA-processing endoribonuclease" (RMRP) was over-expressed in tumor samples, particularly those from patients with poorer overall survival outcomes. Along with follow up RNA in situ hybridization analyses in another patient group, they used a series of cell line and tumor xenograft experiments to demonstrate that RMRP and its SNRPA1 partner protein can dampen p53 activity through MDM2-mediated ubiquitination and degradation, leading to enhanced CRC growth. The authors note that RMRP also appeared to be expressed in response to PARP inhibitor treatment, while targeting the lncRNA appeared to boost PARP inhibitor response in colorectal cancer cells.

The Scan

International Team Proposes Checklist for Returning Genomic Research Results

Researchers in the European Journal of Human Genetics present a checklist to guide the return of genomic research results to study participants.

Study Presents New Insights Into How Cancer Cells Overcome Telomere Shortening

Researchers report in Nucleic Acids Research that ATRX-deficient cancer cells have increased activity of the alternative lengthening of telomeres pathway.

Researchers Link Telomere Length With Alzheimer's Disease

Within UK Biobank participants, longer leukocyte telomere length is associated with a reduced risk of dementia, according to a new study in PLOS One.

Nucleotide Base Detected on Near-Earth Asteroid

Among other intriguing compounds, researchers find the nucleotide uracil, a component of RNA sequences, in samples collected from the near-Earth asteroid Ryugu, as they report in Nature Communications.