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Current Opinion in Genetics & Development

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https://www.readbyqxmd.com/read/29245064/circrnas-in-cancer
#1
REVIEW
Ines Lucia Patop, Sebastian Kadener
Exonic circular RNAs (circRNAs) are mostly generated from exons of protein-coding genes and, in many cases, are more abundant that the linear product from their hosting gene. Certain circRNAs are very abundant in the brain and in non-dividing cells; and many also show physiological-specific and tissue-specific expression. Moreover, recent work has demonstrated that some circRNAs are functional. Lately an important number of research articles have pointed a relation between cancer and certain circRNAs. In this review, we describe general advances in the field regarding circRNA biogenesis and functions in relationship with cancer...
December 12, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29216518/expanding-horizons-new-roles-for-non-canonical-rna-binding-proteins-in-cancer
#2
REVIEW
Samantha Moore, Aino I Järvelin, Ilan Davis, Gareth L Bond, Alfredo Castello
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...
December 4, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29179096/cross-talk-between-protein-synthesis-energy-metabolism-and-autophagy-in-cancer
#3
REVIEW
Lisa M Lindqvist, Kristofferson Tandoc, Ivan Topisirovic, Luc Furic
Translation is a pivotal step in the regulation of gene expression as well as one of the most energy consuming processes in the cell. Dysregulation of translation caused by the aberrant function of upstream signaling pathways and/or perturbations in the expression or function of components of the translation machinery is frequent in cancer. In this review, we discuss emerging findings that highlight hitherto unappreciated aspects of signaling to the translation apparatus with the particular focus on emerging connections between protein synthesis, autophagy and energy homeostasis in cancer...
November 24, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29175729/rna-regulons-in-cancer-and-inflammation
#4
REVIEW
Laura Simone Bisogno, Jack Donald Keene
Gene expression is the fundamental driving force that coordinates normal cellular processes and adapts to dysfunctional conditions such as oncogenic development and progression. While transcription is the basal process of gene expression, RNA transcripts are both the templates that encode proteins as well as perform functions that directly regulate diverse cellular processes. All levels of gene expression require coordination to optimize available resources, but how global gene expression drives cancers or responds to disrupting oncogenic mutations is not understood...
November 22, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29169064/eukaryotic-initiation-factor-4f-sidestepping-resistance-mechanisms-arising-from-expression-heterogeneity
#5
REVIEW
Jennifer Chu, Santiago Ramon Y Cajal, Nahum Sonenberg, Jerry Pelletier
There is enormous diversity in the genetic makeup and gene expression profiles between and within tumors. This heterogeneity leads to phenotypic variation and is a major mechanism of resistance to molecular targeted therapies. Here we describe a conceptual framework for targeting eukaryotic initiation factor (eIF) 4F in cancer-an essential complex that drives and promotes multiple Cancer Hallmarks. The unique nature of eIF4F and its druggability bypasses several of the heterogeneity issues that plague molecular targeted drugs developed for cancer therapy...
November 20, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29153484/translation-initiation-factors-and-their-relevance-in-cancer
#6
REVIEW
Columba de la Parra, Beth A Walters, Phillip Geter, Robert J Schneider
Deregulation of several translation initiation factors occurs in numerous types of cancers. Translation initiation factors are not merely ancillary players in cancer development and progression, but rather, they are key participants in cellular transformation and tumor development. In fact, the altered expression of translation initiation factors is involved in cancer cell survival, metastasis and tumor angiogenesis. Although the exact mechanisms remain to be fully characterized, translation initiation factors comprise novel targets for pharmacologic intervention...
November 15, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29153483/crosstalks-between-translation-and-metabolism-in-cancer
#7
REVIEW
Stefano Biffo, Nicola Manfrini, Sara Ricciardi
Albeit cancer patients' heterogeneity, all tumor cells have alterations of both metabolism and translation. The simplest explanation for this common feature is that several oncogenes coordinate a translational and metabolic reprogramming that is necessary for tumor cells to thrive. Overall, at least three oncogenic pathways, namely c-Myc, RAS and PI3K-mTOR, are known to affect both translation and metabolism by stimulating glycolysis and protein synthesis. The crosstalk between metabolite production and the translational machinery is, instead, less understood...
November 15, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29136527/targeting-splicing-abnormalities-in-cancer
#8
REVIEW
Anant A Agrawal, Lihua Yu, Peter G Smith, Silvia Buonamici
Recently splicing has been recognized as a key pathway in cancer. Although aberrant splicing has been shown to be a consequence of mutations or the abnormal expression of splicing factors (trans-effect changes) or mutations in the splicing sequences (cis-effect mutations), the connections between aberrant splicing and cancer initiation or progression are still not well understood. Here we review the mutational landscape of splicing factors in cancer and associated splicing consequences, along with the most important examples of the therapeutic approaches targeting the spliceosome currently being investigated in oncology...
November 11, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29128695/insights-from-structures-of-cancer-relevant-pre-mrna-splicing-factors
#9
REVIEW
Clara L Kielkopf
Pre-mRNA splicing factors recognize consensus signals within preliminary transcripts, and as cogs of the spliceosome machine, orchestrate the excision and rejoining of pre-mRNA regions for gene expression. Large-scale sequencing has demonstrated that mutations in key genes encoding pre-mRNA splicing factors are common among myeloid neoplasms and also occur in a variety of other cancers. This revelation offers new therapeutic opportunities to target pre-mRNA splicing vulnerabilities in hematologic and other malignancies...
November 9, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29127844/the-role-of-a-to-i-rna-editing-in-cancer-development
#10
REVIEW
Xiaoyan Xu, Yumeng Wang, Han Liang
Adenosine-to-inosine (A-to-I) RNA editing is the most common type of post-transcriptional nucleotide modification in humans, which is catalyzed in ADAR enzymes. Recent genomic studies have revealed thousands of altered RNA editing events in various cancer tissues, leading to diverse functional consequences. A critical role of individual A-to-I RNA editing events in cancer has been reported. Here, we review the current state of our knowledge on key A-to-I RNA editing events in coding and non-coding regions for their roles in cancer development and discuss their potential clinical utility...
November 8, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29121514/nonsense-mediated-mrna-decay-and-cancer
#11
REVIEW
Maximilian W Popp, Lynne E Maquat
Nonsense-mediated mRNA decay (NMD) is a conserved mRNA surveillance pathway that cells use to ensure the quality of transcripts and to fine-tune transcript abundance. The role of NMD in cancer development is complex. In some cases, tumors have exploited NMD to downregulate gene expression by apparently selecting for mutations causing destruction of key tumor-suppressor mRNAs. In other cases, tumors adjust NMD activity to adapt to their microenvironment. Understanding how particular tumors exploit NMD for their benefit may augment the development of new therapeutic interventions...
November 7, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29102895/insights-into-visual-pigment-adaptation-and-diversity-from-model-ecological-and-evolutionary-systems
#12
REVIEW
Frances E Hauser, Belinda Sw Chang
Sensory systems provide valuable insight into the evolution of molecular mechanisms underlying organismal anatomy, physiology, and behaviour. Visual pigments, which mediate the first step in visual transduction, offer a unique window into the relationship between molecular variation and visual performance, and enhance our understanding of how ecology, life history, and physiology may shape genetic variation across a variety of organisms. Here we review recent work investigating vertebrate visual pigments from a number of perspectives...
November 2, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29100211/chimeric-rnas-and-their-implications-in-cancer
#13
REVIEW
Zi Li, Fujun Qin, Hui Li
Chimeric RNAs have been believed to be solely produced by gene fusions resulting from chromosomal rearrangement, thus unique features of cancer. Detected chimeric RNAs have also been viewed as surrogates for the presence of gene fusions. However, more and more research has demonstrated that chimeric RNAs in general are not a hallmark of cancer, but rather widely present in non-cancerous cells and tissues. At the same time, they may be produced by other mechanisms other than chromosomal rearrangement. The field of non-canonical chimeric RNAs is still in its infancy, with many challenges ahead, including the lack of a unified terminology...
October 31, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29100210/post-transcriptional-control-of-stress-responses-in-cancer
#14
REVIEW
Robert F Harvey, Anne E Willis
The processes by which the canonical protein synthesis machinery is modified by environmental stresses to allow healthy cells to respond to external conditions to maintain homeostasis, are frequently hijacked by tumour cells to enhance their survival. Two major stress response pathways that play a major role in this regard are the unfolded protein response (UPR) and the DNA damage response (DDR). Recent data have shown that key proteins which coordinate post-transcriptional control, and which are regulated by signalling through the UPR and DDR, are upregulated in cancers and that targeting these proteins/pathways will provide new therapeutic avenues for cancer treatments...
October 28, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29100209/ribosome-biogenesis-and-cancer-basic-and-translational-challenges
#15
REVIEW
Xosé R Bustelo, Mercedes Dosil
Increasing evidence suggests that alterations in ribosome biogenesis (RiBi) confer competitive advantages to cancer cells. This has led to the discovery of regulatory layers mediated by signaling proteins, oncoproteins, and tumor suppressors whose deregulation leads to increased RiBi rates in cancer cells. In addition to boosting protein synthesis, these alterations probably contribute to shape the protumorigenic proteome of cancer cells. Mutations negatively affecting RiBi are also unexpectedly found in some spontaneous and ribosomopathy-associated tumors...
October 26, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29080552/the-role-of-alternative-splicing-in-cancer-drug-resistance
#16
REVIEW
Zahava Siegfried, Rotem Karni
One of the major challenges in cancer treatment today is that many patients develop resistance to the therapeutic agents, resulting in treatment failure. Alternative splicing can significantly alter the coding region of drug targets. Here, we highlight several reports that provide key examples of alternative splicing events that occur in various cancers and play a role in resistance to cancer therapy. These examples present prime targets for future study and development of splicing modulation therapy. Modulation of alternative splicing has recently been approved as treatment for several diseases, although not yet for cancer...
October 25, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29203086/editorial-overview-making-evolutionary-sense-of-everything
#17
EDITORIAL
David L Stern, Eric Haag
No abstract text is available yet for this article.
December 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29120735/the-rewiring-of-transcription-circuits-in-evolution
#18
REVIEW
Alexander D Johnson
The binding of transcription regulators to cis-regulatory sequences is a key step through which all cells regulate expression of their genes. Due to gains and losses of cis-regulatory sequences and changes in the transcription regulators themselves, the binding connections between regulators and their target genes rapidly change over evolutionary time and constitute a major source of biological novelty. This review covers recent work, carried out in a wide range of species, that addresses the overall extent of these evolutionary changes, their consequences, and some of the molecular mechanisms that lie behind them...
December 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28915487/genetic-backgrounds-and-hidden-trait-complexity-in-natural-populations
#19
REVIEW
Téo Fournier, Joseph Schacherer
Dissecting the genetic basis of natural phenotypic variation is a major goal in biology. We know that most traits are strongly heritable. However, their genetic architecture is a long-standing question, which is unfortunately confounded by the lack of complete knowledge of the genetic components as well as their phenotypic effect in a specific genetic background. Many genetic variants are known to affect phenotypes but the same functional variant can have a different effect on the phenotype in different individuals of the same species...
December 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29059583/darwin-was-right-where-now-for-experimental-evolution
#20
REVIEW
Paul B Rainey, Philippe Remigi, Andrew D Farr, Peter A Lind
Over the last two decades interest in direct realisation of evolutionary process and the possibilities presented by real time evolution experiments with microbes have escalated. Long-term selection experiments with bacteria have made increasingly transparent the process of evolution by natural selection. In this short article we consider what next for the field and do so by highlighting two areas of interest: the genotype-to-phenotype map and the constraints it imposes on evolution, and studies on major evolutionary transitions and in particular the importance of selection working over more than one timescale...
October 20, 2017: Current Opinion in Genetics & Development
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