Nuestros investigadores

Maite Huarte Martínez

Publicaciones científicas más recientes (desde 2010)

Autores: Pazo, A.; Perez-Gonzalez, A.; Oliveros, J. C. ; et al.
ISSN 1664-042X  Vol. 10  Nº 92  2019 
hCLE/C14orf166/RTRAF, DDX1, and HSPC117 are components of cytoplasmic mRNA-transporting granules kinesin-associated in dendrites. They have also been found in cytoplasmic ribosome-containing RNA granules that transport specific mRNAs halted for translation until specific neuronal signals renders them accessible to the translation machinery. hCLE associates to DDX1, HSPC117, and FAM98B in HEK293T cells and all four proteins bind to cap analog-containing resins. Competition and elution experiments indicate that binding of hCLE complex to cap resins is independent of elF4E; the cap-binding factor needed for translation. Purified hCLE free of its associated proteins binds cap with low affinity suggesting that its interacting proteins modulate its cap association. hCLE silencing reduces hCLE accumulation and that of its interacting proteins and decreases mRNA translation. hCLE-associated RNAs have been isolated and sequenced; RNAs involved in mRNA translation are specifically associated. The data suggest that RNA granules may co-transport RNAs encoding proteins involved in specific functions together with RNAs that encode proteins needed for the translation of these specific RNAs and indicate an important role for hCLE modulating mRNA translation.
Autores:  et al.
ISSN 1043-0342  Vol. 30  Nº 11  2019  págs. A2 - A2
Autores: Huarte, Maite, (Autor de correspondencia)
ISSN 1465-7392  Vol. 20  Nº 4  2018  págs. 371 - 372
Autores: Huarte, Maite, (Autor de correspondencia)
Revista: CELL
ISSN 0092-8674  Vol. 173  Nº 6  2018  págs. 1318 - 1319
The role of the noncoding genome in cancer biology is continually expanding. Cho et al. reveal a new and unexpected mechanism for the regulation of MYC expression mediated by the promoter sequence of its neighbor gene PVT1. This DNA element acts as a promoter-enhancer competitor and a candidate tumor suppressor.'
Autores: Mondal, T.; Juvvuna, P. K.; Kirkeby, A.; et al.
ISSN 1535-6108  Vol. 33  Nº 3  2018  págs. 417 - +
Trait-associated loci often map to genomic regions encoding long noncoding RNAs (lncRNAs), but the role of these lncRNAs in disease etiology is largely unexplored. We show that a pair of sense/antisense lncRNA (6p22lncRNAs) encoded by CASC15 and NBAT1 located at the neuroblastoma (NB) risk-associated 6p22.3 locus are tumor suppressors and show reduced expression in high-risk NBs. Loss of functional synergy between 6p22lncRNAs results in an undifferentiated state that is maintained by a gene-regulatory network, including SOX9 located on 17q, a region frequently gained in NB. 6p22lncRNAs regulate SOX9 expression by controlling CHD7 stability via modulating the cellular localization of USP36, encoded by another 17q gene. This regulatory nexus between 6p22.3 and 17q regions may lead to potential NB treatment strategies.
Autores: Aldave, G.; González, María Soledad; Rubio, A; et al.
ISSN 1522-8517  Vol. 20  Nº 7  2018  págs. 930 - 941
Background: Glioblastoma, the most aggressive primary brain tumor, is genetically heterogeneous. Alternative splicing (AS) plays a key role in numerous pathologies, including cancer. The objectives of our study were to determine whether aberrant AS could play a role in the malignant phenotype of glioma and to understand the mechanism underlying its aberrant regulation. Methods: We obtained surgical samples from patients with glioblastoma who underwent 5-aminolevulinic fluorescence-guided surgery. Biopsies were taken from the tumor center as well as from adjacent normal-appearing tissue. We used a global splicing array to identify candidate genes aberrantly spliced in these glioblastoma samples. Mechanistic and functional studies were performed to elucidate the role of our top candidate splice variant, BAF45d, in glioblastoma. Results: BAF45d is part of the switch/sucrose nonfermentable complex and plays a key role in the development of the CNS. The BAF45d/6A isoform is present in 85% of over 200 glioma samples that have been analyzed and contributes to the malignant glioma phenotype through the maintenance of an undifferentiated cellular state. We demonstrate that BAF45d splicing is mediated by polypyrimidine tract-binding protein 1 (PTBP1) and that BAF45d regulates PTBP1, uncovering a reciprocal interplay between RNA splicing regulation and transcription. Conclusions: Our data indicate that AS is a mechanism that contributes to the malignant phenotype of glioblastoma. Understanding the consequences of this biological process will uncover new therapeutic targets for this devastating disease.
Autores: Torres-Bayona, S.; Aldaz, P.; Auzmendi-Iriarte, J.; et al.
ISSN 2045-2322  Vol. 8  Nº 12746  2018 
Long non-coding RNAs (LncRNAs) have emerged as a relevant class of genome regulators involved in a broad range of biological processes and with important roles in tumor initiation and malignant progression. We have previously identified a p53-regulated tumor suppressor signature of LncRNAs (PR-LncRNAs) in colorectal cancer. Our aim was to identify the expression and function of this signature in gliomas. We found that the expression of the four PR-LncRNAs tested was high in human low-grade glioma samples and diminished with increasing grade of disease, being the lowest in glioblastoma samples. Functional assays demonstrated that PR-LncRNA silencing increased glioma cell proliferation and oncosphere formation. Mechanistically, we found an inverse correlation between PR-LncRNA expression and SOX1, SOX2 and SOX9 stem cell factors in human glioma biopsies and in glioma cells in vitro. Moreover, knock-down of SOX activity abolished the effect of PR-LncRNA silencing in glioma cell activity. In conclusion, our results demonstrate that the expression and function of PR-LncRNAs are significantly altered in gliomagenesis and that their activity is mediated by SOX factors. These results may provide important insights into the mechanisms responsible for glioblastoma pathogenesis.
Autores: Huarte, Maite, (Autor de correspondencia)
ISSN 1474-760X  Vol. 18  2017 
A major shift in our understanding of genome regulation has emerged recently. It is now apparent that the majority of cellular transcripts do not code for proteins, and many of them are long noncoding RNAs (lncRNAs). Increasingly, studies suggest that lncRNAs regulate gene expression through diverse mechanisms. We review emerging mechanistic views of lncRNAs in gene regulation in the cell nucleus. We discuss the functional interactions that lncRNAs establish with other molecules as well as the relationship between lncRNA transcription and function. While some of these mechanisms are specific to lncRNAs, others might be shared with other types of genes.
Autores: Huarte, Maite;
ISSN 1538-4101  Vol. 16  Nº 2  2017  págs. 151 - 152
Autores: Huarte, Maite;
ISSN 1078-8956  Vol. 23  Nº 10  2017  págs. 1122 - 1123
Two recent studies show that 'silent' variants can modulate regulatory circuits, including those in noncoding RNAs, affecting cancer predisposition and drug sensitivity.
Autores: Li, X.L. ; Subramanian, M. ; Jones, M. F. ; et al.
ISSN 2211-1247  Vol. 20  Nº 10  2017  págs. 2408 - 2423
Basal p53 levels are tightly suppressed under normal conditions. Disrupting this regulation results in elevated p53 levels to induce cell cycle arrest, apoptosis, and tumor suppression. Here, we report the suppression of basal p53 levels by a nuclear, p53-regulated long noncoding RNA that we termed PURPL (p53 upregulated regulator of p53 levels). Targeted depletion of PURPL in colorectal cancer cells results in elevated basal p53 levels and induces growth defects in cell culture and in mouse xenografts. PURPL associates with MYBBP1A, a protein that binds to and stabilizes p53, and inhibits the formation of the p53-MYBBP1A complex. In the absence of PURPL, MYBBP1A interacts with and stabilizes p53. Silencing MYBBP1A significantly rescues basal p53 levels and proliferation in PURPL-deficient cells, suggesting that MYBBP1A mediates the effect of PURPL in regulating p53. These results reveal a p53-PURPL auto-regulatory feedback loop and demonstrate a role for PURPL in maintaining basal p53 levels.
Autores: Marin-Bejar, O.; Gonzalez, J.; et al.
ISSN 1474-760X  Vol. 18  2017  págs. 202
BACKGROUND: It is now obvious that the majority of cellular transcripts do not code for proteins, and a significant subset of them are long non-coding RNAs (lncRNAs). Many lncRNAs show aberrant expression in cancer, and some of them have been linked to cell transformation. However, the underlying mechanisms remain poorly understood and it is unknown how the sequences of lncRNA dictate their function. RESULTS: Here we characterize the function of the p53-regulated human lncRNA LINC-PINT in cancer. We find that LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells. A cross-species analysis identifies a highly conserved sequence element in LINC-PINT that is essential for its function. This sequence mediates a specific interaction with PRC2, necessary for the LINC-PINT-dependent repression of a pro-invasion signature of genes regulated by the transcription factor EGR1. CONCLUSIONS: Our findings support a conserved functional co-dependence between LINC-PINT and PRC2 and lead us to propose a new mechanism where the lncRNA regulates the availability of free PRC2 at the proximity of co-regulated genomic loci.
Autores: Terradas, M.; Martin, M.; Repulles, J.; et al.
ISSN 0033-7587  Vol. 186  Nº 6  2016  págs. 549 - 558
High-and low-dose X rays are used in medicine as therapeutic and diagnostic tools, respectively. While the cellular response to high-dose radiation is well known, studies on the effects of low-dose radiation and its ability to trigger a proper DNA damage response have had contradictory results. The functions of many signaling and effector proteins of the DNA damage response (DDR) have been described, and are attributed to well-known DDR pathways. However, there has been little known about the contribution of long noncoding RNAs (lncRNAs) to DDR, although there is recent evidence that lncRNAs may be associated with almost all biological functions, including DDR. In this work, we investigated the participation of lncRNAs in the response to different X-ray doses. By microarray analysis, we observed that in human breast epithelial cells, distinct sets of coding and noncoding transcripts are differentially regulated after moderate-and high-dose irradiation compared to those regulated after low-dose irradiation. While the modulated coding and noncoding genes at low doses relate to cell signaling pathways, those affected by moderate and high doses are mostly enriched for cell cycle regulation and apoptotic pathways. Quantification using qPCR of the lncRNAs identified by microarrays allowed the validation of 75% of those regulated at the higher doses. These results indicate that lncRNA expression is regulated by ionizing radiation and that this expression is dose dependent. (C) 2016 by Radiation Research Society
Autores: Huarte, Maite;
ISSN 2159-3337  Vol. 23  Nº 1  2013  págs. 15-20
Long non-coding RNAs (lncRNAs) have emerged as one of the largest and more diverse classes of cellular transcripts. The growing evidence suggests that lncRNAs are key regulatory molecules present at virtually every level of cellular physiology, and their alterations are associated with multiple human diseases. Here we provide a general overview of the known roles of lncRNAs in different diseases, as well as their imminent application as biomarkers and therapeutic targets. We also discuss the challenges and possible strategies for these clinical applications. It is unquestionable that our knowledge of lncRNAs not only adds a new dimension to the molecular architecture of human disease, but also opens up a whole new range of opportunities for treatment.