Different proteins associate with the nascent RNA and the RNA polymerase (RNAP) to catalyze the transcription cycle and RNA export. If these processes are not properly controlled, the nascent RNA can thread back and hybridize to the DNA template forming R-loops capable of stalling replication, leading to DNA breaks. Given the transcriptional promiscuity of the genome, which leads to large amounts of RNAs from mRNAs to different types of ncRNAs, these can become a major threat to genome integrity if they form R-loops. Consequently, cells have evolved nuclear factors to prevent this phenomenon that includes THO, a conserved eukaryotic complex acting in transcription elongation and RNA processing and export that upon inactivation causes genome instability linked to R-loop accumulation. click here We revise and discuss here the biological relevance of THO and a number of RNA helicases, including the THO partner UAP56/DDX39B, as a paradigm of the cellular mechanisms of cotranscriptional R-loop prevention.Heterochromatin is a classic context for studying the mechanisms of chromatin organization. At the core of a highly conserved type of heterochromatin is the complex formed between chromatin methylated on histone H3 lysine 9 and HP1 proteins. This type of heterochromatin plays central roles in gene repression, genome stability, and nuclear mechanics. Systematic studies over the last several decades have provided insight into the biophysical mechanisms by which the HP1-chromatin complex is formed. Here, we discuss these studies together with recent findings indicating a role for phase separation in heterochromatin organization and function. We suggest that the different functions of HP1-mediated heterochromatin may rely on the increasing diversity being uncovered in the biophysical properties of HP1-chromatin complexes.Eukaryotic gene expression requires the cumulative activity of multiple molecular machines to synthesize and process newly transcribed pre-messenger RNA. Introns, the noncoding regions in pre-mRNA, must be removed by the spliceosome, which assembles on the pre-mRNA as it is transcribed by RNA polymerase II (Pol II). The assembly and activity of the spliceosome can be modulated by features including the speed of transcription elongation, chromatin, post-translational modifications of Pol II and histone tails, and other RNA processing events like 5′-end capping. Here, we review recent work that has revealed cooperation and coordination among co-transcriptional processing events and speculate on new avenues of research. We anticipate new mechanistic insights capable of unraveling the relative contribution of coupled processing to gene expression.The RNA exosome was originally discovered in yeast as an RNA-processing complex required for the maturation of 5.8S ribosomal RNA (rRNA), one of the constituents of the large ribosomal subunit. The exosome is now known in eukaryotes as the major 3′-5′ RNA degradation machine involved in numerous processing, turnover, and surveillance pathways, both in the nucleus and the cytoplasm. Yet its role in maturing the 5.8S rRNA in the pre-60S ribosomal particle remains probably the most intricate and emblematic among its functions, as it involves all the RNA unwinding, degradation, and trimming activities embedded in this macromolecular complex. Here, we propose a comprehensive mechanistic model, based on current biochemical and structural data, explaining the dual functions of the nuclear exosome-the constructive versus the destructive mode.Purpose To assess the associations among different optical coherence tomography (OCT) structural and angiography quantitative metrics used to characterise the choroid in healthy subjects. Methods In this cross-sectional study, macular structural OCT and OCT angiography (OCTA) images were acquired from healthy subjects. The main outcome measures were (i) choriocapillaris (CC) flow deficits percentage (FD%), (ii) choroidal luminal (LA) and stromal (SA) areas and (iii) choroidal vascularity index (CVI), which was calculated as the LA divided by the total choroidal area. These measurements were generated using previously published algorithms and were separately computed in the foveal and extrafoveal regions. Results Eighty-five eyes from 85 subjects (44 males, 41 females) were included in the analysis. Mean±SD age was 47.9±22.4 years (range 19.0 to 85.0 years). Linear regression analysis displayed no significant associations between CC FD% and other parameters (LA, SA and CVI). Importantly, non-linear regression analysis showed that the relations of LA and SA to CC FD% were all best fitted by a quadratic function. Compared with the linear models, the use of the quadratic function allowed a relative increase in the R2 coefficients. No significant non-linear associations were found between CC FD% and CVI. Conclusion Based on our models, changes in the luminal and stromal areas in the choroid lead to an initial increase in CC perfusion. Subsequently, further increases in LA and SA amounts are accompanied by a progressive increment in CC FD%.Aims To assess the diagnostic accuracy (DTA) of optical coherence tomography (OCT) for detecting glaucoma by systematically searching and appraising systematic reviews (SRs) on this issue. Methods We searched a database of SRs in eyes and vision maintained by the Cochrane Eyes and Vision United States on the DTA of OCT for detecting glaucoma. Two authors working independently screened the records, abstracted data and assessed the risk of bias using the Risk of Bias in Systematic Reviews checklist. We extracted quantitative DTA estimates as well as qualitative statements on their relevance to practice. Results We included four SRs published between 2015 and 2018. These SRs included between 17 and 113 studies on OCT for glaucoma diagnosis. Two reviews were at low risk of bias and the other two had two to four domains at high or unclear risk of bias with concerns on applicability. The two reliable SRs reported the accuracy of average retinal nerve fibre layer (RNFL) thickness and found a sensitivity of 0.69 (0.63 to 0.73) and 0.78 (0.74 to 0.83) and a specificity of 0.94 (0.93 to 0.95) and 0.93 (0.92 to 0.95) in 57 and 50 studies, respectively. Only one review included a clear specification of the clinical pathway. Both reviews highlighted the limitations of primary DTA studies on this topic. Conclusions The quality of published DTA reviews on OCT for diagnosing glaucoma was mixed. Two reliable SRs found moderate sensitivity at high specificity for average RNFL thickness in diagnosing manifest glaucoma. Our overview suggests that the methodological quality of both primary and secondary DTA research on glaucoma is in need of improvement.