Structural basis of RNA polymerase III transcription initiation.

RNA polymerase (Pol) III transcribes essential non-coding RNAs, including the entire pool of transfer RNAs, the 5S ribosomal RNA and the U6 spliceosomal RNA, and is often deregulated in cancer cells. The initiation of gene transcription by Pol III requires the activity of the transcription factor TFIIIB to form a transcriptionally active Pol III preinitiation complex (PIC). Here we present electron microscopy reconstructions of Pol III PICs at 3.4-4.0 Å and a reconstruction of unbound apo-Pol III at 3.1 Å. TFIIIB fully encircles the DNA and restructures Pol III. In particular, binding of the TFIIIB subunit Bdp1 rearranges the Pol III-specific subunits C37 and C34, thereby promoting DNA opening. The unwound DNA directly contacts both sides of the Pol III cleft. Topologically, the Pol III PIC resembles the Pol II PIC, whereas the Pol I PIC is more divergent. The structures presented unravel the molecular mechanisms underlying the first steps of Pol III transcription and also the general conserved mechanisms of gene transcription initiation

Cam morphology and inguinal pathologies: is there a possible connection?

Background: To analyse the prevalences of the cam and pincer morphologies in a cohort of patients with groin pain syndrome caused by inguinal pathologies. Materials and methods: Forty-four patients (40 men and 4 women) who suffered from groin pain syndrome were enrolled in the study. All the patients were radiographically and clinically evaluated following a standardised protocol established by the First Groin Pain Syndrome Italian Consensus Conference on Terminology, Clinical Evaluation and Imaging Assessment in Groin Pain in Athlete. Subsequently, all of the subjects underwent a laparoscopic repair of the posterior inguinal wall. Results: The study demonstrated an association between the cam morphology and inguinal pathologies in 88.6% of the cases (39 subjects). This relationship may be explained by noting that the cam morphology leads to biomechanical stress at the posterior inguinal wall level. Conclusions: Athletic subjects who present the cam morphology may be considered a population at risk of developing inguinal pathologies. Level of evidence: Level IV, Observational cross-sectional study

Intraspecific concerted evolution of the rDNA ITS1 in anopheles farauti sensu stricto (Diptera: Culicidae) reveals recent patterns of population structure

We examined the intraindividual variation present in the first ribosomal internal transcribed spacer (ITS1) of Anopheles farauti to determine the level of divergence among populations for this important malarial vector. We isolated 187 clones from 70 individuals and found regional variation among four internal tandem repeats. The data were partitioned prior to analysis given the presence of a paralogous ITS2 sequence, called the 5'-subrepeat, inserted in the ITS1 of most clones. A high level of homogenization and population differentiation was observed for this repeat, which indicates a higher rate of turnover relative to the adjacent 'core' region. Bayesian analysis was performed using several substitutional models on both a combined and a partitioned data set. On the whole, the ITS1 phylogeny and geographic origin of the samples appear to be congruent. Some interesting exceptions indicate the spread of variant repeats between populations and the retention of ancestral polymorphism. Our data clearly demonstrate concerted evolution at the intraspecific level despite intraindividual variation and a complex internal repeat structure from a species that occupies a continuous coastal distribution. A high rate of genomic turnover in combination with a high level of sequence divergence appears to be a major factor leading to its concerted evolution within these populations