RESUMEN
The Database of Intrinsically Disordered Proteins (DisProt, URL: https://disprot.org) is the major repository of manually curated annotations of intrinsically disordered proteins and regions from the literature. We report here recent updates of DisProt version 9, including a restyled web interface, refactored Intrinsically Disordered Proteins Ontology (IDPO), improvements in the curation process and significant content growth of around 30%. Higher quality and consistency of annotations is provided by a newly implemented reviewing process and training of curators. The increased curation capacity is fostered by the integration of DisProt with APICURON, a dedicated resource for the proper attribution and recognition of biocuration efforts. Better interoperability is provided through the adoption of the Minimum Information About Disorder (MIADE) standard, an active collaboration with the Gene Ontology (GO) and Evidence and Conclusion Ontology (ECO) consortia and the support of the ELIXIR infrastructure.
Asunto(s)
Bases de Datos de Proteínas , Proteínas Intrínsecamente Desordenadas/metabolismo , Anotación de Secuencia Molecular , Programas Informáticos , Secuencia de Aminoácidos , ADN/genética , ADN/metabolismo , Conjuntos de Datos como Asunto , Ontología de Genes , Humanos , Internet , Proteínas Intrínsecamente Desordenadas/química , Proteínas Intrínsecamente Desordenadas/genética , Unión Proteica , ARN/genética , ARN/metabolismoRESUMEN
Previous studies suggested that both maladaptive stress response and circadian dysregulation might have a role in the background of migraine. However, effects of circadian genes on migraine have not been tested yet. In the present study, we investigated the main effect of rs10462028 of the circadian locomotor output cycles kaput (CLOCK) gene and its interaction with different stress factors on migraine. In our cross-sectional study 2,157 subjects recruited from Manchester and Budapest completed the ID-Migraine questionnaire to detect migraine type headaches (migraineID). Additional stress factors were assessed by a shortened version of the Childhood Trauma Questionnaire, the List of Threatening Experiences questionnaire, and a validated questionnaire to identify financial difficulties. Rs10462028 showed no main genetic effect on migraineID. However, chronic stress indexed by financial difficulties showed a significant interaction effect with rs10462028 (p = 0.006 in recessive model) on migraineID. This result remained significant after correction for lifetime bipolar and unipolar depression and was replicated in both subsamples, although only a trend effect was reached after Bonferroni-correction, which is the strictest correction not considering interdependences. Childhood adversity (CHA) and Recent negative life events (RLE) showed no significant gene × stress interaction with rs10462028. In addition, in silico analysis demonstrated that the genetic region tagged by rs10462028 alters the binding of several miRNAs. Our exploratory study suggests that variations in the CLOCK gene, with moderating effect on gene function through miRNA binding, in interaction with financial difficulties might influence the risk of migraine-type headaches. Thus, financial hardship as a chronic stress factor may affect migraine through altering circadian rhythms.
RESUMEN
In nonsense-mediated mRNA decay (NMD), large protein complexes cooperate to trigger degradation of mRNA with a premature termination codon. Due to the extreme variation in the size and topology of its mRNA substrate, the structural underpinning of the fidelity of NMD is little understood. Based on bioinformatic predictions, we suggest that fly-casting mechanisms enabled by long disordered regions in NMD complexes are exploited for the underlying effective long-range communication.