Hu Antigen R (HuR) Protein Structure, Function and Regulation in Hepatobiliary Tumors

Hepatobiliary tumors are a group of primary malignancies encompassing the liver, the intra- and extra-hepatic biliary tracts, and the gall bladder. Within the liver, hepatocellular carcinoma (HCC) is the most common type of primary cancer, which is, also, representing the third-most recurrent cause of cancer-associated death and the sixth-most prevalent type of tumor worldwide, nowadays. Although less frequent, cholangiocarcinoma (CCA) is, currently, a fatal cancer with limited therapeutic options. Here, we review the regulatory role of Hu antigen R (HuR), a ubiquitous member of the ELAV/Hu family of RNA-binding proteins (RBPs), in the pathogenesis, progression, and treatment of HCC and CCA. Overall, HuR is proposed as a valuable diagnostic and prognostic marker, as well as a therapeutic target in hepatobiliary cancers. Therefore, novel therapeutic approaches that can selectively modulate HuR function appear to be highly attractive for the clinical management of these types of tumors.España Ministerio de Ciencia, Innovación y Universidades (MICINN), integrated in the Plan Estatal de Investigación Científica y Técnica e Innovación, grant numbers PID2020-117116RB-I00 (to M.L.M.-C.) and PGC2018-096049-B-I00Gobierno de Andalucía, grant numbers BIO-198, US-1254317, US-1257019, P18-FR-3487, and P18-HO-4091Fondo Europeo de Desarrollo Regional (FEDER) (to MLM-C and I.D.-M.); and the La Caixa Foundation Program, grant number HR17-00601 (to M.L.M.-C.).España Ministerio de Educación, Cultura y Deporte, grant number FPU016/0151

Ornelas_et al_MAXENT_Lampornis_amethystinus

Lampornis amethystinus_MAXENT_File: coordinates longitude and latitude of Lampornis amethystinus

Ornelas_et al_IMa_SMOSvsTMVB_mt+micros

Amethyst-throated populations from the Sierra Madre Oriental versus amethyst-throated populations along the Trans-Mexican Volcanic Belt of Lampornis amethystinus for mitochondrial markers (ND2 and cytochrome b) and microsatellites

Ornelas_et al_IMa_AMETvsBLUE_mt+micros

Amethyst-throated (Sierra Madre Oriental and Trans-Mexican Volcanic Belt) versus blue-throated (Sierra Madre del Sur) populations of Lampornis amethystinus for mitochondrial markers (ND2 and cytochrome b) and microsatellites

Ornelas_et al_IMa_WESTvsEAST_mt+micros

Amethyst-throated (incl. blue-throated) populations west of the Istmus of Tehuantepec versus amethyst-throated populations east of the Isthmus of Tehuantepec of Lampornis amethystinus for mitochondrial markers (ND2 and cytochrome b) and microsatellites

Ornelas_et al_DIYABC_Genotypes_mito

Ornelas_et al_DIYABC_Genotypes_mito text-formatted DIYABC data file containing microsatellite genotypes and mitochondrial ND2 and cytochrome b concatenated sequences of populations of Lampornis amethystinus

Ornelas_et al_microsatellites_info

Microsatellite sizing for 126 samples of Lampornis amethystinus hummingbirds genotyped at eigth autosomal microsatellite loci previously designed for Campylopterus curvipennis (Cacu16-1 and Cacu17-2; Molecular Ecology Resources Primer Development Consortium et al. 2010; GenBank accession nos. GQ294539–GQ294550) and Selasphorus platycercus (HUMB2, HUMB3, HUMB9, HUMB10, HUMBB11 and HUMB15Oyler-McCance et al. 2011; HQ316946–HQ316955). Microsatellite sizing for each loci consists in 3 digits (e.g. 216 for L32 Malinche, Tlax. at loci Cacu 16-1)

Ornelas_et al_DIYABC_models_header

Ornelas_et al_DIYABC_models_header text-formatted DIYABC reftableHeader file containing scenarios, priors and summary statistics used in the DIYABC analysis

Post-translational Control of RNA-Binding Proteins and Disease-Related Dysregulation

Cell signaling mechanisms modulate gene expression in response to internal and external stimuli. Cellular adaptation requires a precise and coordinated regulation of the transcription and translation processes. The post-transcriptional control of mRNA metabolism is mediated by the so-called RNA-binding proteins (RBPs), which assemble with specific transcripts forming messenger ribonucleoprotein particles of highly dynamic composition. RBPs constitute a class of trans-acting regulatory proteins with affinity for certain consensus elements present in mRNA molecules. However, these regulators are subjected to post-translational modifications (PTMs) that constantly adjust their activity to maintain cell homeostasis. PTMs can dramatically change the subcellular localization, the binding affinity for RNA and protein partners, and the turnover rate of RBPs. Moreover, the ability of many RBPs to undergo phase transition and/or their recruitment to previously formed membrane-less organelles, such as stress granules, is also regulated by specific PTMs. Interestingly, the dysregulation of PTMs in RBPs has been associated with the pathophysiology of many different diseases. Abnormal PTM patterns can lead to the distortion of the physiological role of RBPs due to mislocalization, loss or gain of function, and/or accelerated or disrupted degradation. This Mini Review offers a broad overview of the post-translational regulation of selected RBPs and the involvement of their dysregulation in neurodegenerative disorders, cancer and other pathologies.Junta de Andalucía BIO-198, US-1254317, US-1257019, P18-FR-3487, P18-HO-4091Ministerio de Ciencia, Innovación y Universidades PGC2018-096049-BMinisterio de Educación, Cultura y Deporte FPU016/0151