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Trends in Genetics: TIG

Mar Soto, Jonne A Raaijmakers, René H Medema
Chromosome segregation errors are an important source of genomic diversification that promote tumor heterogeneity and evolution. However, the aneuploidy induced by chromosome missegregations causes cellular stress at many levels, raising the question of how segregation errors can be tolerated in cancer. Additionally, we now know that chromosome segregation errors can lead to activation of the innate immune system, producing yet another challenge for chromosomally unstable cells. These observations imply that several liabilities are encountered during tumor evolution, which could potentially be exploited for cancer therapies...
February 8, 2019: Trends in Genetics: TIG
Nadee Nissanka, Michal Minczuk, Carlos T Moraes
Mitochondrial DNA (mtDNA) encodes a subset of genes which are essential for oxidative phosphorylation. Deletions in the mtDNA can ablate a number of these genes and result in mitochondrial dysfunction, which is associated with bona fide mitochondrial disorders. Although mtDNA deletions are thought to occur as a result of replication errors or following double-strand breaks, the exact mechanism(s) behind deletion formation have yet to be determined. In this review we discuss the current knowledge about the fate of mtDNA following double-strand breaks, including the molecular players which mediate the degradation of linear mtDNA fragments and possible mechanisms of recircularization...
January 25, 2019: Trends in Genetics: TIG
Robert L Grossman
Data commons collate data with cloud computing infrastructure and commonly used software services, tools, and applications to create biomedical resources for the large-scale management, analysis, harmonization, and sharing of biomedical data. Over the past few years, data commons have been used to analyze, harmonize, and share large-scale genomics datasets. Data ecosystems can be built by interoperating multiple data commons. It can be quite labor intensive to curate, import, and analyze the data in a data commons...
January 25, 2019: Trends in Genetics: TIG
John F Beckmann, Manon Bonneau, Hongli Chen, Mark Hochstrasser, Denis Poinsot, Hervé Merçot, Mylène Weill, Mathieu Sicard, Sylvain Charlat
Wolbachia bacteria inhabit the cells of about half of all arthropod species, an unparalleled success stemming in large part from selfish invasive strategies. Cytoplasmic incompatibility (CI), whereby the symbiont makes itself essential to embryo viability, is the most common of these and constitutes a promising weapon against vector-borne diseases. After decades of theoretical and experimental struggle, major recent advances have been made toward a molecular understanding of this phenomenon. As pieces of the puzzle come together, from yeast and Drosophila fly transgenesis to CI diversity patterns in natural mosquito populations, it becomes clearer than ever that the CI induction and rescue stem from a toxin-antidote (TA) system...
January 23, 2019: Trends in Genetics: TIG
Vanessa Tsui, Wayne Crismani
Fanconi anemia (FA) is a life-threatening syndrome characterized by bone marrow failure and cancer predispositions. The past two decades have seen an explosion of data in the FA field, both in humans and other organisms, following the cloning of 22 FA genes. A common but notably understudied clinical feature of the disease is the reduced fertility of individuals with FA. This review focuses on the known causes of reduced fertility in FA, and integrates them with the emerging role of the FA pathway in double-strand break (DSB) repair at meiosis in a variety of organisms, as well as providing future directions for research and diagnostics...
January 22, 2019: Trends in Genetics: TIG
Laura B Chipman, Amy E Pasquinelli
miRNAs are small RNAs that guide Argonaute proteins to specific target mRNAs to repress their translation and stability. Canonically, miRNA targeting is reliant on base pairing of the seed region, nucleotides 2-7, of the miRNA to sites in mRNA 3' untranslated regions. Recently, the 3' half of the miRNA has gained attention for newly appreciated roles in regulating target specificity and regulation. In addition, the extent of pairing to the miRNA 3' end can influence the stability of the miRNA itself. These findings highlight the importance of sequences beyond the seed in controlling the function and existence of miRNAs...
January 9, 2019: Trends in Genetics: TIG
Jorge Ruiz-Orera, M Mar Albà
The translatome can be defined as the sum of the RNA sequences that are translated into proteins in the cell by the ribosomal machinery. Until recently, it was generally assumed that the translatome was essentially restricted to evolutionary conserved proteins encoded by the set of annotated protein-coding genes. However, it has become increasingly clear that it also includes small regulatory open reading frames (ORFs), functional micropeptides, de novo proteins, and the pervasive translation of likely nonfunctional proteins...
December 31, 2018: Trends in Genetics: TIG
Hongyun Qi, Brendan D Price, Tovah A Day
Although stress-induced synthesis of mono(ADP-ribose) (mADPr) and poly(ADP-ribose) (pADPr) conjugates by pADPr polymerase (PARP) enzymes has been studied extensively, the removal and degradation of pADPr, as well as the fate of ADPr metabolites, have received less attention. The observations that stress-induced pADPr undergoes rapid turnover, and that deficiencies in ADPr degradation phenocopy loss of pADPr synthesis, suggest that ADPr degradation is fundamentally important to the cellular stress response. Recent work has identified several distinct families of pADPr hydrolases that can degrade pADPr to release pADPr or mADPr into the cytoplasm...
December 27, 2018: Trends in Genetics: TIG
Hippokratis Kiaris
The living stock collections represent an indispensable resource for life scientists. Their uninterrupted operation should combine high quality standards, cost-effectiveness, wide accessibility, and sustainability. Mammalian stock collections, especially those involving diversified animals, face some unique challenges that may disrupt their smooth operation if not addressed.
December 23, 2018: Trends in Genetics: TIG
Joanna Kufel, Pawel Grzechnik
Transcribing RNA Polymerase II interacts with multiple factors that orchestrate maturation and stabilisation of messenger RNA. For the majority of noncoding RNAs, the polymerase complex employs entirely different strategies, which usually direct the nascent transcript to ribonucleolytic degradation. However, some noncoding RNA classes use endo- and exonucleases to achieve functionality. Here we review processing of small nucleolar RNAs that are transcribed by RNA Polymerase II as precursors, and whose 5' and 3' ends undergo processing to release mature, functional molecules...
December 15, 2018: Trends in Genetics: TIG
Andrew J Saurin, Marie Claire Delfini, Corinne Maurel-Zaffran, Yacine Graba
No abstract text is available yet for this article.
December 7, 2018: Trends in Genetics: TIG
Ananda Kishore Mukherjee, Shalu Sharma, Shantanu Chowdhury
The role of non-duplex DNA, the guanine-quadruplex structure in particular, is becoming widely appreciated. Increasing evidence in the last decade implicates quadruplexes in important processes such as transcription and replication. Interestingly, more recent work suggests roles for quadruplexes, in association with quadruplex-interacting proteins, in epigenetics through both DNA and histone modifications. Here, we review the effect of the quadruplex structure on post-replication epigenetic memory and quadruplex-induced promoter DNA/histone modifications...
December 4, 2018: Trends in Genetics: TIG
Zhaobin Dong, Martin Alexander, George Chuck
As an economically important model crop plant, rich in genetic resources, maize has been useful for uncovering the genetic pathways responsible for domestication and plant improvement. However, several of the pathways that have been shown by recent studies to be important for domestication and/or yield in other grasses function differently in maize. In several cases, this unexpectedly wide functional divergence between genes from closely related grasses appears to be due to alternative modes of regulation rather than to simple differences in protein function...
November 30, 2018: Trends in Genetics: TIG
Hunter B Fraser
No abstract text is available yet for this article.
November 30, 2018: Trends in Genetics: TIG
Xinwen Zhang, J J Emerson
No abstract text is available yet for this article.
November 29, 2018: Trends in Genetics: TIG
Yi Xiang See, Benny Zhengjie Wang, Melissa J Fullwood
Chromatin interactions regulate gene expression by bringing distal regulatory elements, such as super-enhancers, to promoters in close spatial proximity. It has been recognized that in cancer, chromatin interactions can be dysregulated, leading to aberrant oncogene expression. Chromatin interactions may potentially serve as biomarkers, or be modulated via CRISPR therapy and small molecule inhibitors against transcription. However, these methods face challenges that must be resolved and raise questions for further research...
February 2019: Trends in Genetics: TIG
Marc S Halfon
Transcriptional enhancers play a major role in regulating metazoan gene expression. Recent developments in genomics and next-generation sequencing have accelerated and revitalized the study of this important class of sequence elements. Increased interest and attention, however, has also led to troubling trends in the enhancer literature. In this Opinion, I describe some of these issues and show how they arise from shifting and nonuniform enhancer definitions, and genome-era biases. I discuss how they can lead to interpretative errors and an unduly narrow focus on certain aspects of enhancer biology to the potential exclusion of others...
February 2019: Trends in Genetics: TIG
Gregg Duester
No abstract text is available yet for this article.
February 2019: Trends in Genetics: TIG
Michele Trabucchi
Different methods have recently been developed to understand the subcellular localization and role of microRNAs (miRNAs) as well as small RNAs associated with Argonaute (AGO) proteins. The heterogeneity of the protein complexes associated with miRNAs, along with their subcellular localization, provides clues into their biochemical mechanism of function. Subcellular diversity indicates that miRNAs localized to different cellular regions could have different functions, including transcriptional regulation on chromatin or post-transcriptional control, providing global regulation of gene expression by miRNAs...
January 2019: Trends in Genetics: TIG
Matías Montes, Brianne L Sanford, Daniel F Comiskey, Dawn S Chandler
Alternative splicing of pre-mRNA increases genetic diversity, and recent studies estimate that most human multiexon genes are alternatively spliced. If this process is not highly regulated and accurate, it leads to mis-splicing events, which may result in proteins with altered function. A growing body of work has implicated mis-splicing events in a range of diseases, including cancer, neurodegenerative diseases, and muscular dystrophies. Understanding the mechanisms that cause aberrant splicing events and how this leads to disease is vital for designing effective therapeutic strategies...
January 2019: Trends in Genetics: TIG
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