Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted some time this week.
Researchers from Ohio State University and the University of California, San Diego, search for transfer RNA (tRNA) fragments involved in chronic lymphocytic leukemia (CLL) development. Using small RNA sequencing on CD19+ B cell samples from 10 indolent CLL cases, 10 aggressive cases of CLL, and eight unaffected controls, the team tracked the expression of tRNA-derived short non-coding RNA (tsRNA) fragments and mature tRFs stemming from tRNA precursor sequences. Their analyses uncovered thousands of tsRNAs or mature tRFs at increased or diminished expression in CLL, including tRNA fragments found at higher-than-usual levels in the aggressive CLL cases. From such findings, the authors suggest "tsRNAs and mature tRFs, [two] classes of small non-coding RNAs, may be associated with the development of CLL."
A Yale School of Medicine-led team describes sites in the genome that appear to be particularly sensitive to ultraviolet radiation in human melanocyte cells. The researchers profiled UV-exposed primary human melanocyte and fibroblast cells with adductSeq and freSeq methods aimed at identifying and tallying rare single-based changes associated with UV light exposure, uncovering mutation hotspots, particularly near genes and in the melanocyte cells. "This paper reports that human melanocytes, responsible for skin and hair color, contain over 2,000 such genomic sites that are up to 170-fold more sensitive than the average site," the authors write. "These sites occur at specific locations near genes, so may let UV radiation drive direct changes in cell physiology rather than act through rare mutations."
Investigators at China's Northeastern University, the Dana-Farber Cancer Institute, and elsewhere explore essential cis-regulatory transcription factor binding sites and related factors, dubbed "cistromes," in the human genome by systematically knocking out FOXA1 and CTCF transcription factor binding sites in breast cancer or prostate cancer cells with the help of CRISPR-Cas9 gene editing. Using this screening strategy, the team focused in on FOXA1 binding sites required for fitness at gene enhancer sites, for example, along with enhancer- and topologically associated domain (TAD) boundary sites where CTCF binding appeared to be essential. "These efforts not only reveal how the key transcription factors and their cistromes regulate cell essentiality in hormone-dependent cancers," the authors report, "but also highlight an efficient approach to investigate the functions of non-coding regions of the genome."