Expanding horizons: new roles for non-canonical RNA-binding proteins in cancer

Cancer development involves the stepwise accumulation of genetic lesions that overcome the normal regulatory pathways that prevent unconstrained cell division and tissue growth. Identification of the genetic changes that cause cancer has long been the subject of intensive study, leading to the identification of several RNA-binding proteins (RBPs) linked to cancer. Cross-reference of the complement of RBPs recently identified by RNA interactome capture with cancer-associated genes and biological processes led to the identification of a set of 411 proteins with potential implications in cancer biology. These involve a broad spectrum of cellular processes including response to stress, metabolism and cell adhesion. Future studies should aim to understand these proteins and their connection to cancer from an RNA-centred perspective, holding the promise of new mechanistic understanding of cancer formation and novel approaches to diagnosis and treatment

A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets

Exosomal miRNA transfer is a mechanism for cell-cell communication that is important in the immune response, in the functioning of the nervous system and in cancer. Syncrip/hnRNPQ is a highly conserved RNA-binding protein that mediates the exosomal partition of a set of miRNAs. Here, we report that Syncrip's amino-terminal domain, which was previously thought to mediate protein-protein interactions, is a cryptic, conserved and sequence-specific RNA-binding domain, designated NURR (N-terminal unit for RNA recognition). The NURR domain mediates the specific recognition of a short hEXO sequence defining Syncrip exosomal miRNA targets, and is coupled by a non-canonical structural element to Syncrip's RRM domains to achieve high-affinity miRNA binding. As a consequence, Syncrip-mediated selection of the target miRNAs implies both recognition of the hEXO sequence by the NURR domain and binding of the RRM domains 5′ to this sequence. This structural arrangement enables Syncrip-mediated selection of miRNAs with different seed sequences. © 2018 The Author(s)

Areale potenziale dei boschi a Carpinus betulus nell\u2019alta valle del B\ufbt (Italia NE) e descrizione della nuova associazione Phyteumato zahlbruckneri-Carpinetum betuli

In questo lavoro viene presentata un\u2019analisi della distribuzione dei boschi a Carpinus betulus nell\u2019alta Valle del B\ufbt (UD), al fine di sviluppare un modello della distribuzione potenziale di una tipologia vegetazionale in un\u2019area complessa dal punto di vista geomorfologico tramite un\u2019applicazione GIS. Lo studio effettuato ha preso in considerazione i carpineti, consorzi forestali di elevato valore naturalistico-paesaggistico minacciati dalla storica azione dell\u2019uomo sul territorio. Il modello della distribuzione potenziale \ue8 stato creato mediante l\u2019incrocio di dati geomorfologici e climatici in ambiente GIS. Il confronto tra la distribuzione reale, la distribuzione potenziale e i diversi tematismi ha evidenziato come l\u2019area di diffusione dei carpineti sia molto ridotta rispetto all\u2019area potenzialmente adatta a questi boschi e ha permesso di individuare i principali fattori naturali ed antropici che possono influenzare la distribuzione attuale dei carpineti nell\u2019area di studio. Lo studio ha inoltre portato alla descrizione di una nuova associazione a Carpinus betulus che rientra nel gruppo dei carpineti a carattere meridionale gi\ue0 descritti per le Alpi nella zona del Friuli Venezia Giulia e Slovenia e completa il quadro cenologico della specie a livello regionale. Phyteumato zahlbruckneri-Carpinetum betuli \ue8 una cenosi a carattere subacidofilo subcontinentale diffusa nella regione forestale mesalpica della Carnia centrale nella fascia submontana e montana inferiore su suoli moderatamente acidi impostati su substrati silicatici alterabili paleozoici, in un\u2019area con buone precipitazioni atmosferiche (1600-1800 mm annui), temperature medie annue di 8-11\ub0C ed estati miti e piuttosto piovose, interessate dall\u2019influenza mitigatrice delle correnti provenienti dal mare; la cenosi rientra nell\u2019Habitat Natura 2000 91L0 - Querco-carpineti illirici (Erythronio-Carpinion). Viene presentata tutta la serie dinamica di cui il nuovo carpineto rappresenta la fase finale

A brave new world of RNA-binding proteins

RNA-binding proteins (RBPs) are typically thought of as proteins that bind RNA through one or multiple globular RNA-binding domains (RBDs) and change the fate or function of the bound RNAs. Several hundred such RBPs have been discovered and investigated over the years. Recent proteome-wide studies have more than doubled the number of proteins implicated in RNA binding and uncovered hundreds of additional RBPs lacking conventional RBDs. In this Review, we discuss these new RBPs and the emerging understanding of their unexpected modes of RNA binding, which can be mediated by intrinsically disordered regions, protein–protein interaction interfaces and enzymatic cores, among others. We also discuss the RNA targets and molecular and cellular functions of the new RBPs, as well as the possibility that some RBPs may be regulated by RNA rather than regulate RNA

HIV rev-isited

The human immunodeficiency virus type 1 (HIV-1) proteome is expressed from alternatively spliced and unspliced genomic RNAs. However, HIV-1 RNAs that are not fully spliced are perceived by the host machinery as defective and are retained in the nucleus. During late infection, HIV-1 bypasses this regulatory mechanism by expression of the Rev protein from a fully spliced mRNA. Once imported into the nucleus, Rev mediates the export of unprocessed HIV-1 RNAs to the cytoplasm, leading to the production of the viral progeny. While regarded as a canonical RNA export factor, Rev has also been linked to HIV-1 RNA translation, stabilization, splicing and packaging. However, Rev's functions beyond RNA export have remained poorly understood. Here, we revisit this paradigmatic protein, reviewing recent data investigating its structure and function. We conclude by asking: what remains unknown about this enigmatic viral protein

System-wide analyses of the fission yeast poly(A)+ RNA interactome reveal insights into organization and function of RNA–protein complexes

Large RNA-binding complexes play a central role in gene expression and orchestrate production, function, and turnover of mRNAs. The accuracy and dynamics of RNA–protein interactions within these molecular machines are essential for their function and are mediated by RNA-binding proteins (RBPs). Here, we show that fission yeast whole-cell poly(A)+ RNA–protein crosslinking data provide information on the organization of RNA–protein complexes. To evaluate the relative enrichment of cellular RBPs on poly(A)+ RNA, we combine poly(A)+ RNA interactome capture with a whole-cell extract normalization procedure. This approach yields estimates of in vivo RNA-binding activities that identify subunits within multiprotein complexes that directly contact RNA. As validation, we trace RNA interactions of different functional modules of the 3′ end processing machinery and reveal additional contacts. Extending our analysis to different mutants of the RNA exosome complex, we explore how substrate channeling through the complex is affected by mutation. Our data highlight the central role of the RNA helicase Mtl1 in regulation of the complex and provide insights into how different components contribute to engagement of the complex with substrate RNA. In addition, we characterize RNA-binding activities of novel RBPs that have been recurrently detected in the RNA interactomes of multiple species. We find that many of these, including cyclophilins and thioredoxins, are substoichiometric RNA interactors in vivo. Because RBPomes show very good overall agreement between species, we propose that the RNA-binding characteristics we observe in fission yeast are likely to apply to related proteins in higher eukaryotes as well

A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets.

Exosomal miRNA transfer is a mechanism for cell–cell communication that is important in the immune response, in the functioning of the nervous system and in cancer. Syncrip/hnRNPQ is a highly conserved RNA-binding protein that mediates the exosomal partition of a set of miRNAs. Here, we report that Syncrip’s amino-terminal domain, which was previously thought to mediate protein–protein interactions, is a cryptic, conserved and sequence-specific RNA-binding domain, designated NURR (N-terminal unit for RNA recognition). The NURR domain mediates the specific recognition of a short hEXO sequence defining Syncrip exosomal miRNA targets, and is coupled by a non-canonical structural element to Syncrip’s RRM domains to achieve high-affinity miRNA binding. As a consequence, Syncrip-mediated selection of the target miRNAs implies both recognition of the hEXO sequence by the NURR domain and binding of the RRM domains 5′ to this sequence. This structural arrangement enables Syncrip-mediated selection of miRNAs with different seed sequences

Programa Integral de Tecnologías de Información y Comunicación en la Universidad Nacional de Córdoba, propuestas para el eje temático Software Libre

Este trabajo tiene como objetivo realizar propuestas para fomentar la difusión del software libre en la Universidad Nacional de Córdoba dentro del marco del Programa Integral de Tecnologías de Información y Comunicaciones recientemente aprobado. Se coincide que uno de los ámbitos más favorables para el ecosistema del software libre son los organismos de educación y la administración pública. Diversos estudios nos dicen que las herramientas FLOSS tienen una ecuación favorable cuando se las compara con los productos de software comercial equivalentes; esta ecuación favorable está basada no sólo variables técnicas y económicas, sino también en aspectos socio-políticos de importancia estratégica para el desarrollo científico.Sociedad Argentina de Informática e Investigación Operativ

Uncovering viral RNA-host cell interactions on a proteome-wide scale

RNA viruses interact with a wide range of cellular RNA-binding proteins (RBPs) during their life cycle. The prevalence of these host–virus interactions has been highlighted by new methods that elucidate the composition of viral ribonucleoproteins (vRNPs). Applied to 11 viruses so far, these approaches have revealed hundreds of cellular RBPs that interact with viral (v)RNA in infected cells. However, consistency across methods is limited, raising questions about methodological considerations when designing and interpreting these studies. Here, we discuss these caveats and, through comparing available vRNA interactomes, describe RBPs that are consistently identified as vRNP components and outline their potential roles in infection. In summary, these novel approaches have uncovered a new universe of host–virus interactions holding great therapeutic potential