Rat1 promotes premature transcription termination at R-loops.

Certain DNA sequences can adopt a non-B form in the genome that interfere with DNA-templated processes, including transcription. Among the sequences that are intrinsically difficult to transcribe are those that tend to form R-loops, three-stranded nucleic acid structures formed by a DNA-RNA hybrid and the displaced ssDNA. Here we compared the transcription of an endogenous gene with and without an R-loop-forming sequence inserted.

Characterization of Autochthonous Strains from the Cecal Content of Creole Roosters for a Potential Use as Probiotics.

Five strains (CLP2, CLP3, CLP4, CLP5, and CLP6) were isolated from the cecal content of Creole roosters fed without antibiotic growth promoters. Biochemical and morphological tests (negative catalase and oxidase) confirmed the presence of lactic acid bacteria. Additionally, considering the 16s RNA, (CLP2, CLP3, CLP5, and CLP6) and (CLP4) were identified.

Histone H3E73Q and H4E53A mutations cause recombinogenic DNA damage.

The stability and function of eukaryotic genomes is closely linked to histones and to chromatin structure. The state of the chromatin not only affects the probability of DNA to undergo damage but also DNA repair. DNA damage can result in genetic alterations and subsequent development of cancer and other genetic diseases.

The THO Complex as a Paradigm for the Prevention of Cotranscriptional R-Loops.

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.

R-Loops as Promoters of Antisense Transcription.

The study by Tan-Wong et al. (2019) in this issue of Molecular Cell reveals a capacity of R-loops to promote antisense transcription expanding our view of the features that a DNA region may have to act as a promoter.

Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instability.

THO/TREX is a conserved complex with a role in messenger ribonucleoprotein biogenesis that links gene expression and genome instability. Here, we show that human THO interacts with MFAP1 (microfibrillar-associated protein 1), a spliceosome-associated factor. Interestingly, MFAP1 depletion impairs cell proliferation and genome integrity, increasing γH2AX foci and DNA breaks.

Increased Working Memory Load in a Dual-Task Design Impairs Nonverbal Social Encoding in Children with High and Low Attention-Deficit/Hyperactivity Disorder Symptoms.

Children with attention-deficit/hyperactivity disorder (ADHD) are known to have difficulty with peer relations, though the mechanisms by which these children struggle with interpersonal relationships are not well known. The current study examined the relation between working memory (WM) and the encoding of nonverbal social cues using a dual-task paradigm tested in children with High and Low ADHD symptoms. A total of 40 children were recruited (20 High ADHD; 20 Low ADHD) and completed computerized tasks of social encoding and WM in both single- and dual-task conditions.

What causes an RNA-DNA hybrid to compromise genome integrity?

Transcription is a source of genome instability that stimulates mutation and recombination. Part of the damage produced by transcription is mediated by R-loops, non-B DNA structures that normally form by the re-annealing of the nascent RNA with the template DNA outside the catalytic center of the RNA polymerase, displacing the non-template strand. Recent discoveries have revealed that R-loops might not be harmful by themselves.

Social Functioning in Youth with Attention-Deficit/Hyperactivity Disorder and Sluggish Cognitive Tempo.

The current review summarizes the research to date on social functioning for youth with attention-deficit/hyperactivity disorder (ADHD) with a focus on three key domains: peer rejection, friendship, and social information processing. The review extends past reviews by examining the research to date on how the presence of sluggish cognitive tempo (SCT) symptoms, a common correlate of ADHD, affects the social presentation of youth with ADHD. Overall, youth with ADHD show significant difficulty with peer rejection, forming and maintaining friendships, and abnormalities in how they process and respond to social information.

Yra1-bound RNA-DNA hybrids cause orientation-independent transcription-replication collisions and telomere instability.

R loops are an important source of genome instability, largely due to their negative impact on replication progression. Yra1/ALY is an abundant RNA-binding factor conserved from yeast to humans and required for mRNA export, but its excess causes lethality and genome instability. Here, we show that, in addition to ssDNA and ssRNA, Yra1 binds RNA-DNA hybrids in vitro and, when artificially overexpressed, can be recruited to chromatin in an RNA-DNA hybrid-dependent manner, stabilizing R loops and converting them into replication obstacles in vivo.

Sleep, Internalizing Problems, and Social Withdrawal: Unique Associations in Clinic-Referred Youth With Elevated Sluggish Cognitive Tempo Symptoms.

We compared clinic-referred youth with ADHD + sluggish cognitive tempo (SCT; = 34), ADHD Only ( = 108), and SCT Only ( = 22) on demographics, co-occurring symptomatology, comorbid diagnoses, and social functioning. In total, 164 youth (age = 6-17 years, = 9.97) and their parent(s) presented to an outpatient clinic for a psychoeducational assessment.

An EEG Study of Children With and Without ADHD Symptoms: Between-Group Differences and Associations With Sluggish Cognitive Tempo Symptoms.

We examined differences between those with and without ADHD symptoms on resting state electroencephalography (EEG) indices and unique relations with sluggish cognitive tempo (SCT) symptoms. Children with ADHD symptoms ( = 21) and healthy controls ( = 20) were assessed using rating scales, a neuropsychological task measuring sustained attention and inhibitory control, and EEG activity during a resting state period. Between-group, correlational, and regression analyses were conducted.

Histone Mutants Separate R Loop Formation from Genome Instability Induction.

R loops have positive physiological roles, but they can also be deleterious by causing genome instability, and the mechanisms for this are unknown. Here we identified yeast histone H3 and H4 mutations that facilitate R loops but do not cause instability. R loops containing single-stranded DNA (ssDNA), versus RNA-DNA hybrids alone, were demonstrated using ssDNA-specific human AID and bisulfite.

Immediate effect of laryngeal manual therapy in dysphonic individuals.

Purposes: To investigate the immediate effect of Laryngeal Manual Therapy (LMT) in musculoskeletal pain, in voice and sensations referred to individuals with behavioral dysphonia and individuals without it.

Methods: 30 individuals ranging from 18 to 45 years old were selected and sorted into two groups: the dysphonic group (DG) - 15 individuals with functional or organofunctional dysphonia, and the control group (CG) - 15 individuals without vocal complaints and with non-impaired voices. The individuals answered a pain questionnaire and their voices were subsequently registered.

ADHD Dimensions and Sluggish Cognitive Tempo Symptoms in Relation to Self-Report and Laboratory Measures of Neuropsychological Functioning in College Students.

Objective: This study examined ADHD and sluggish cognitive tempo (SCT) symptoms in relation to self-report and laboratory measures of neuropsychological functioning in college students.

Method: College students ( N = 298, aged 17-25, 72% female) completed self-reports of ADHD, SCT, depression, sleep, functional impairment, and executive functioning (EF). Participants also completed a visual working memory task, a Stroop test, and the Conners' Continuous Performance Test-II (CPT-II).

R loops are linked to histone H3 S10 phosphorylation and chromatin condensation.

R loops are transcription byproducts that constitute a threat to genome integrity. Here we show that R loops are tightly linked to histone H3 S10 phosphorylation (H3S10P), a mark of chromatin condensation. Chromatin immunoprecipitation (ChIP)-on-chip (ChIP-chip) analyses reveal H3S10P accumulation at centromeres, pericentromeric chromatin, and a large number of active open reading frames (ORFs) in R-loop-accumulating yeast cells, better observed in G1.

New clues to understand the role of THO and other functionally related factors in mRNP biogenesis.

Coupling of transcription with mRNA processing and export has been shown to be relevant to efficient gene expression. A number of studies have determined that THO/TREX, a nuclear protein complex conserved from yeast to humans, plays an important role in mRNP biogenesis connecting transcription elongation, mRNA export and preventing genetic instability. Recent data indicates that THO could be relevant to different mRNA processing steps, including the 3'-end formation, transcript release and export.

A novel assay identifies transcript elongation roles for the Nup84 complex and RNA processing factors.

To clarify the role of a number of mRNA processing factors in transcription elongation, we developed an in vivo assay for direct analysis of elongation on chromatin. The assay relies on two substrates containing two G-less cassettes separated by either a long and GC-rich or a short and GC-poor DNA sequence (G-less-based run-on (GLRO) assay). We demonstrate that PAF, THSC/TREX-2, SAGA, the exosome component Rrp6 and two subunits of cleavage factor IA (Rna14 and Rna15) are required for efficient transcription elongation, in contrast to some results obtained using other assays.

Yeast Sen1 helicase protects the genome from transcription-associated instability.

Sen1 of S. cerevisiae is a known component of the NRD complex implicated in transcription termination of nonpolyadenylated as well as some polyadenylated RNA polymerase II transcripts. We now show that Sen1 helicase possesses a wider function by restricting the occurrence of RNA:DNA hybrids that may naturally form during transcription, when nascent RNA hybridizes to DNA prior to its packaging into RNA protein complexes.

The interface between transcription and mRNP export: from THO to THSC/TREX-2.

Eukaryotic gene expression is a multilayer process covering transcription to post-translational protein modifications. As the nascent pre-mRNA emerges from the RNA polymerase II (RNAPII), it is packed in a messenger ribonucleoparticle (mRNP) whose optimal configuration is critical for the normal pre-mRNA processing and mRNA export, mRNA integrity as well as for transcription elongation efficiency. The interplay between transcription and mRNP formation feeds forward and backward and involves a number of conserved factors, from THO to THSC/TREX-2, which in addition have a unique impact on transcription-dependent genome instability.

Fail-safe transcriptional termination for protein-coding genes in S. cerevisiae.

Transcription termination of RNA polymerase II (Pol II) on protein-coding genes in S. cerevisiae relies on pA site recognition by 3' end processing factors. Here we demonstrate the existence of two alternative termination mechanisms that rescue polymerases failing to disengage from the template at pA sites.

Nuclear roadblocks for mRNA export.

The THO complex and Sub2 RNA helicase have been shown to function in both transcription and mRNA processing. Rougemaille et al. (2008) now uncover evidence that THO/Sub2 coordinates mRNA processing and nuclear export.

Budding yeast RNA polymerases I and II employ parallel mechanisms of transcriptional termination.

Both RNA polymerase I and II (Pol I and Pol II) in budding yeast employ a functionally homologous "torpedo-like" mechanism to promote transcriptional termination. For two well-defined Pol II-transcribed genes, CYC1 and PMA1, we demonstrate that both Rat1p exonuclease and Sen1p helicase are required for efficient termination by promoting degradation of the nascent transcript associated with Pol II, following mRNA 3' end processing. Similarly, Pol I termination relies on prior Rnt1p cleavage at the 3' end of the pre-rRNA 35S transcript.