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Gene expression, the decoding of DNA information into accessible instructions for protein synthesis, is a complex process in which multiple steps, including transcription, mRNA processing and mRNA export, are regulated by different factors. One of the first steps in this process involves chemical and structural changes in chromatin to allow transcription. For such changes to occur, histone tail and DNA epigenetic modifications foster the binding of transcription factors to promoter regions. The SAGA coactivator complex plays a crucial role in this process by mediating histone acetylation through Gcn5, and histone deubiquitination through Ubp8 enzymes. However, most SAGA subunits interact physically with other proteins beyond the SAGA complex. These interactions could represent SAGA-independent functions or a mechanism to widen SAGA multifunctionality. Among the different mechanisms to perform more than one function, protein moonlighting defines unrelated molecular activities for the same polypeptide sequence. Unlike pleiotropy, where a single gene can affect different phenotypes, moonlighting necessarily involves separate functions of a protein at the molecular level. In this review we describe in detail some of the alternative physical interactions of several SAGA subunits. In some cases, the alternative role constitutes a clear moonlighting function, whereas in most of them the lack of molecular evidence means that we can only define these interactions as promiscuous that require further work to verify if these are moonlighting functions.

Background: Histone H2B deubiquitination is performed by numerous deubiquitinases in eukaryotic cells including Ubp8, the catalytic subunit of the tetrameric deubiquitination module (DUBm: Ubp8; Sus1; Sgf11; Sgf73) of the Spt-Ada-Gcn5 acetyltransferase (SAGA). Ubp8 is linked to the rest of SAGA through Sgf73 and is activated by the adaptors Sus1 and Sgf11. It is unknown if DUBm/Ubp8 might also work in a SAGA-independent manner. Results: Here we report that a tetrameric DUBm is assembled independently of the SAGA-CORE components SPT7, ADA1 and SPT20. In the absence of SPT7, i.e., independent of the SAGA complex, Ubp8 and Sus1 are poorly recruited to SAGA-dependent genes and to chromatin. Notably, cells lacking Spt7 or Ada1, but not Spt20, show lower levels of nuclear Ubp8 than wild-type cells, suggesting a possible role for SAGA-CORE subunits in Ubp8 localization. Last, deletion of SPT7 leads to defects in Ubp8 deubiquitinase activity in in vivo and in vitro assays. Conclusions: Collectively, our studies show that the DUBm tetrameric structure can form without a complete intact SAGA-CORE complex and that it includes full-length Sgf73. However, subunits of this SAGA-CORE influence DUBm association with chromatin, its localization and its activity.

Objetivo: Comparar los efectos de diferentes diseños de lentes intraoculares sobre la función visual de pacientes sometidos a cirugía de cataratas monocular en diferentes condiciones de iluminación. Métodos: Estudio piloto observacional, prospectivo y transversal de 14 ojos de 14 pacientes con edades comprendidas entre los 59 y los 82 años (70,5 ± 8,6), que se sometieron a una cirugía de cristalino con diferentes tipos de lentes intraoculares: Tecnis® Eyhance™ (Johnson&Johnson Surgical Vision, Inc., Santa Ana, CA), la PhysiOL® IsoPure 123™ (BVI Medical/PhysIOL, Lieja, Bélgica) y AcrySof ® IQ Vivity™ (Alcon Laboratories, Inc, Fort Worth TX.). El estudio fue aprobado por el Comité de Ética del Hospital Clínico San Carlos de Madrid. Los sujetos participantes mostraron su acuerdo a colaborar firmando un consentimiento informado. Las pruebas se realizaron transcurrido el día, la semana y mes de la intervención, siendo estos últimos los resultados que se incluyeron en este estudio. Se midió la refracción manifiesta del paciente y la agudeza visual corregida monocularmente en distancia lejana, intermedia y cercana. Estas pruebas se realizaron en condiciones de iluminación fotópica y mesópica. Para el análisis de los datos obtenidos en este estudio se utilizó el software estadístico SPPS versión 28. Resultados: Sólo se obtuvieron valores estadísticamente significativos al comparar la agudeza visual de cerca en condiciones de iluminación fotópica entre las lentes Eyhance y Vivity con un p-valor de 0,013. Mientras que en visión lejana e intermedia, no se obtuvieron diferencias estadísticamente significativas en diferentes condiciones con distintas iluminaciones. Conclusiones: Las tres LIO proporcionaron buenos resultados visuales a distancias lejanas, intermedias y cercanas, tanto en condiciones fotópicas como mesópicas. En general, la lente Isopure 123 proporciona mejor visión en distancia lejana e intermedia, en cambio en cerca la lente que da mejor resultado es la lente Ey

La publicación el 28 de septiembre de 2022 de dos Propuestas de Directiva que abordan aspectos relacionados con los daños ocasionados por sistemas de inteligencia artificial dan pie a interesantes y controvertidas cuestiones. En este trabajo tras exponer aspectos comunes a ambas y establecer también las diferencias, me adentro, en primer lugar, en el estudio de la Propuesta de Directiva de responsabilidad civil extracontractual derivada de la puesta en circulación o en servicio en el mercado de sistemas de inteligencia artificial para concluir, entre otras consideraciones, que se alivia muy poco -si es que lo hace- la carga de la prueba a la víctima. Seguidamente trato algunos aspectos en relación con la Propuesta de Directiva de responsabilidad civil por defectos en los productos en relación con los mismos sistemas que, en este caso, quedarían embebidos en la expresión “programa informático”. Se concluye, entre otros aspectos de interés, que la gran cantidad de conceptos jurídicos indeterminados y las posibilidades de presunciones iuris tantum que deja abiertas la Propuesta (defecto, nexo causal o ambos) no hace fácil la labor del juzgador ni su incorporación a los derechos internos

The inclusion of omic data into constraint-based modeling (CBM) has improved metabolic network characterization of biological models. However, the integration of semi-quantitative metabolomic data into CBM remains challenging. Here, we present MAMBA (Metabolic Adjustment via Multiomic Blocks Aggregation), a CBM approach that enables the use of semi-quantitative metabolomic data together with a gene-centric omic data type (e.g. transcriptomics, ChIP-seq or chromatin accessibility data, among others), and the combination of different time points and conditions. MAMBA outperformed other methods in terms of metabolic network characterization and metabolite prediction accuracy. As a case study, we applied MAMBA to a yeast multiomic dataset with time series design where two different yeast strains where exposed to heat stress. MAMBA captured known biology of heat stress in yeast and identified novel affected metabolic pathways. MAMBA was implemented as an integer linear programming (ILP) problem to guarantee efficient computation, and coded for MATLAB (freely available at github.com/ConesaLab/MAMBA).

RNA-binding proteins (RBPs) participate in all steps of gene expression, underscoring their potential as regulators of RNA homeostasis. We structurally and functionally characterize Mip6, a four-RNA recognition motif (RRM)-containing RBP, as a functional and physical interactor of the export factor Mex67. Mip6-RRM4 directly interacts with the ubiquitin-associated (UBA) domain of Mex67 through a loop containing tryptophan 442. Mip6 shuttles between the nucleus and the cytoplasm in a Mex67-dependent manner and concentrates in cytoplasmic foci under stress. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation experiments show preferential binding of Mip6 to mRNAs regulated by the stress-response Msn2/4 transcription factors. Consistent with this binding, MIP6 deletion affects their export and expression levels. Additionally, Mip6 interacts physically and/or functionally with proteins with a role in mRNA metabolism and transcription such as Rrp6, Xrn1, Sgf73, and Rpb1. These results reveal a novel role for Mip6 in the homeostasis of Msn2/4-dependent transcripts through its direct interaction with the Mex67 UBA domain.