Affinity proteomic dissection of the human nuclear cap-binding complex interactome

A 5',7-methylguanosine cap is a quintessential feature of RNA polymerase II-transcribed RNAs, and a textbook aspect of co-transcriptional RNA processing. The cap is bound by the cap-binding complex (CBC), canonically consisting of nuclear cap-binding proteins 1 and 2 (NCBP1/2). Interest in the CBC has recently renewed due to its participation in RNA-fate decisions via interactions with RNA productive factors as well as with adapters of the degradative RNA exosome. A novel cap-binding protein, NCBP3, was recently proposed to form an alternative CBC together with NCBP1, and to interact with the canonical CBC along with the protein SRRT. The theme of post-transcriptional RNA fate, and how it relates to co-transcriptional ribonucleoprotein assembly, is abundant with complicated, ambiguous, and likely incomplete models. In an effort to clarify the compositions of NCBP1-, 2- and 3-related macromolecular assemblies, we have applied an affinity capture-based interactome screen where the experimental design and data processing have been modified to quantitatively identify interactome differences between targets under a range of experimental conditions. This study generated a comprehensive view of NCBP-protein interactions in the ribonucleoprotein context and demonstrates the potential of our approach to benefit the interpretation of complex biological pathways

The efficacy of high-dose cabergoline treatment of prolactinomas resistant to standard doses: a clinical observation

Hyperprolactinemia (HP) is one of the most common neuroendocrine disorders. In 60% of cases, pathological HP is caused by pituitary prolactin-secreting adenoma. Therapy with agonists of dopamine type 2 receptors (D2 receptor agonists) is a method of choice for the treatment of pathological HP which allows to achieve prolactin normalization and reduction of pituitary adenoma in most cases. However, 15-20% of patients are resistant to D2 receptor agonists, and the question of overcoming this resistance is highly relevant. Different approaches are considered to solve this problem, one - is to increase the dose of D2 receptor agonists up to the maximally tolerated. In this article, we present a clinical observation of a patient with a partial resistance to D2 receptor agonists who demonstrated a good response to treatment with high doses of cabergoline

Assessing impact of changes in human resources features on enterprise activities: simulation model

The need for creating programs of human resources development is shown; the impact of these programs on organizational effectiveness is taken into account. The stages of development tools and HRD programs on the basis of cognitive modelling are disclosed; these stages will help assess the impact of HR-practices on the key indicators of organization activity at the design stage. The method of HR-practices’ pre-selection in professional development of the employees is represented

Mathematical modelling as basis for efficient enterprise management

The choice of the most effective HR- management style at the enterprise is based on modeling various socio-economic situations. The article describes the formalization of the managing processes aimed at the interaction between the allocated management subsystems. The mathematical modelling tools are used to determine the time spent on recruiting personnel for key positions in the management hierarchy selection

Mathematical modelling as basis for efficient enterprise management

The choice of the most effective HR- management style at the enterprise is based on modeling various socio-economic situations. The article describes the formalization of the managing processes aimed at the interaction between the allocated management subsystems. The mathematical modelling tools are used to determine the time spent on recruiting personnel for key positions in the management hierarchy selection

Assessing impact of changes in human resources features on enterprise activities: simulation model

The need for creating programs of human resources development is shown; the impact of these programs on organizational effectiveness is taken into account. The stages of development tools and HRD programs on the basis of cognitive modelling are disclosed; these stages will help assess the impact of HR-practices on the key indicators of organization activity at the design stage. The method of HR-practices’ pre-selection in professional development of the employees is represented

Conserved long-range base pairings are associated with pre-mRNA processing of human genes

The ability of nucleic acids to form double-stranded structures is essential for all living systems on Earth. Current knowledge on functional RNA structures is focused on locally-occurring base pairs. However, crosslinking and proximity ligation experiments demonstrated that long-range RNA structures are highly abundant. Here, we present the most complete to-date catalog of conserved complementary regions (PCCRs) in human protein-coding genes. PCCRs tend to occur within introns, suppress intervening exons, and obstruct cryptic and inactive splice sites. Double-stranded structure of PCCRs is supported by decreased icSHAPE nucleotide accessibility, high abundance of RNA editing sites, and frequent occurrence of forked eCLIP peaks. Introns with PCCRs show a distinct splicing pattern in response to RNAPII slowdown suggesting that splicing is widely affected by co-transcriptional RNA folding. The enrichment of 3'-ends within PCCRs raises the intriguing hypothesis that coupling between RNA folding and splicing could mediate co-transcriptional suppression of premature pre-mRNA cleavage and polyadenylation