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PNAS Papers on Turkish Populations, Pericentromeric Non-Coding RNA, Global Genome Repair

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 international team tallies genetic variation and population structure in present-day Turkey, using a combination of exome and whole-genome sequencing. Based on exome sequences for nearly 2,600 unrelated individuals, and genome sequences for another 773, the researchers put together a "Turkish Variome" spanning almost 10 million previously unappreciated variants, including relatively rare loss-of-function variants, and untangled ancestry patterns in the Turkish population, which appeared to stem from populations in Europe, the Balkans, Caucasus, and Middle East. "Consistent with Turkey's location at the crossroads of many historical population migrations, we find a high level of admixture," they write, noting that the findings "also highlight the importance of population-specific reference panels for increasing the accuracy of imputation, especially for rare variation." GenomeWeb has more on this, here.

Researchers from the Japanese Foundation for Cancer Research and other centers in Japan describe DNA binding, chromatin organization, and gene expression shifts during the process of cellular senescence that appear to stem from alterations involving pericentromeric non-coding RNAs that are typically silenced. "During the aging process, senescent cells secrete inflammatory factors, causing various age-related pathologies," they write. "Thus, controlling the senescence-associated secretory phenotype (SASP) can tremendously benefit human health." With the help of chromatin immunoprecipitation sequencing experiments, ATAC-seq, and other analyses, the team saw signs that SASP-related transcription of pericentromeric non-coding RNA may interfere with CCCTC-binding factor (CTCF) DNA interactions, leading to altered chromosomal accessibility and enhanced inflammation-related gene expression related to aging and cancer risk.

For another paper slated to appear in PNAS this week, a University of Chicago team outlines a role for the RNA methylation-related gene METTL14 in a global genome repair process that helps mute mutagenesis and skin cancer by mending lesions that alter the DNA double helix. Based on immunoprecipitation sequencing, RNA sequencing, and other experiments in human keratinocyte and skin cancer cells, the researchers saw signs that ultraviolet B light can dial down levels of methyltransferase-like 14 gene METTL14, a component of an N6-methyladenosine methyltransferase enzyme "writer complex" that modifies messenger RNA and non-coding RNA, via an autophagy pathway that includes the NBR1 autophagy receptor. "Taken together, these findings demonstrate that METTL14 is a target for selective autophagy and acts as a critical epitranscriptomic mechanism to regulate GGR and suppresses UVB-induced skin tumorigenesis," the authors report, adding that such results "may be translated into potential strategies to improve genome stability and cancer prevention by targeting the METTL14 pathway."