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"Spector, David"
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Ferment : the life-changing power of microbes
Tim Spector is on a mission to bring fermenting into our lives and kitchens. Drawing on the latest science and his own experiments, 'Ferment' is an accessible introduction to the life-changing benefits of fermentation - for beginners and enthusiasts alike. With little more than time, patience and basic equipment, the humblest of ingredients can be transformed into nutritious foods with an astonishing range of benefits for our gut health, immunity and daily mood. Including practical tips and some of his favourite recipes, the book cuts through myths and misunderstanding to help us navigate the fascinating world of ferments and shows how they can help improve our health, our meal times and our planet.
BOOK
Long non-coding RNAs: definitions, functions, challenges and recommendations
Genes specifying long non-coding RNAs (lncRNAs) occupy a large fraction of the genomes of complex organisms. The term ‘lncRNAs’ encompasses RNA polymerase I (Pol I), Pol II and Pol III transcribed RNAs, and RNAs from processed introns. The various functions of lncRNAs and their many isoforms and interleaved relationships with other genes make lncRNA classification and annotation difficult. Most lncRNAs evolve more rapidly than protein-coding sequences, are cell type specific and regulate many aspects of cell differentiation and development and other physiological processes. Many lncRNAs associate with chromatin-modifying complexes, are transcribed from enhancers and nucleate phase separation of nuclear condensates and domains, indicating an intimate link between lncRNA expression and the spatial control of gene expression during development. lncRNAs also have important roles in the cytoplasm and beyond, including in the regulation of translation, metabolism and signalling. lncRNAs often have a modular structure and are rich in repeats, which are increasingly being shown to be relevant to their function. In this Consensus Statement, we address the definition and nomenclature of lncRNAs and their conservation, expression, phenotypic visibility, structure and functions. We also discuss research challenges and provide recommendations to advance the understanding of the roles of lncRNAs in development, cell biology and disease.This Consensus Statement addresses the definition, nomenclature and classification of long non-coding RNAs, and provides a shared viewpoint on their features and functions. The authors also discuss research challenges and provide recommendations to advance our understanding of long non-coding RNAs.
Journal Article
High stakes : a wild cards mosaic novel
Officer Francis, vigilante joker \"The Infamous Black Tongue,\" and ace thief Tesseract are forced by a cold-blooded Baba Yaga into an illegal fight ring as part of her effort to placate a vicious monster from another dimension.
Book
MALAT1 Long Non-Coding RNA: Functional Implications
The mammalian genome is pervasively transcribed and the functional significance of many long non-coding RNA (lncRNA) transcripts are gradually being elucidated. Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) is one of the most well-studied lncRNAs. MALAT1 is a highly conserved nuclear retained lncRNA that is abundantly expressed in cells and tissues and has been shown to play a role in regulating genes at both the transcriptional and post-transcriptional levels in a context-dependent manner. However, Malat1 has been shown to be dispensable for normal development and viability in mice. Interestingly, accumulating evidence suggests that MALAT1 plays an important role in numerous diseases including cancer. Here, we discuss the current state-of-knowledge in regard to MALAT1 with respect to its function, role in diseases, and the potential therapeutic opportunities for targeting MALAT1 using antisense oligonucleotides and small molecules.
Journal Article
Texas hold'em
\"San Antonio, home of the Alamo, is also host to the nation's top high school jazz competition, and the musicians at Xavier Desmond High are excited to outplay their rivals. They are also jokers, kids with strange abilities and even stranger looks. On top of that, well, they are teenagers, apt for mischief, mishaps, and romantic misunderstandings. Michelle Pond, aka The Amazing Bubbles, thinks that her superhero (and supermom) know-how has prepared her to chaperone the event. But when her students start going wayward, she'll soon discover the true meaning of 'Don't mess with Texas'\"--Dust jacket flap.
BOOK
A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression
A growing number of long nuclear‐retained non‐coding RNAs (ncRNAs) have recently been described. However, few functions have been elucidated for these ncRNAs. Here, we have characterized the function of one such ncRNA, identified as metastasis‐associated lung adenocarcinoma transcript 1 (Malat1). Malat1 RNA is expressed in numerous tissues and is highly abundant in neurons. It is enriched in nuclear speckles only when RNA polymerase II‐dependent transcription is active. Knock‐down studies revealed that Malat1 modulates the recruitment of SR family pre‐mRNA‐splicing factors to the transcription site of a transgene array. DNA microarray analysis in Malat1‐depleted neuroblastoma cells indicates that Malat1 controls the expression of genes involved not only in nuclear processes, but also in synapse function. In cultured hippocampal neurons, knock‐down of Malat1 decreases synaptic density, whereas its over‐expression results in a cell‐autonomous increase in synaptic density. Our results suggest that Malat1 regulates synapse formation by modulating the expression of genes involved in synapse formation and/or maintenance.
Malat1 is a long non‐coding RNA that localizes to nuclear speckles, but whose function remains unclear. Here, the Spector and Bessis laboratories show that Malat1 is important for the recruitment of splicing factors to transcription sites, the expression of synaptic genes and as a consequence synaptogenesis.
Journal Article
Direct visualization of the co-transcriptional assembly of a nuclear body by noncoding RNAs
The formation of subnuclear domains, such as the paraspeckles where hyperdited mRNAs are stored, is not well understood. The transcription of the paraspeckle non-coding RNA MEN ɛ/β initiates the recruitment of other components to assemble this nuclear body.
The cell nucleus is a highly compartmentalized organelle harbouring a variety of dynamic membraneless nuclear bodies
1
,
2
,
3
,
4
. How these subnuclear domains are established and maintained is not well understood
5
,
6
,
7
,
8
. Here, we investigate the molecular mechanism of how one nuclear body, the paraspeckle, is assembled and organized. Paraspeckles are discrete ribonucleoprotein bodies found in mammalian cells and implicated in nuclear retention of hyperedited mRNAs
9
,
10
,
11
. We developed a live-cell imaging system that allows for the inducible transcription of Men ɛ/β (also known as Neat1; ref.
12
) noncoding RNAs (ncRNAs) and the direct visualization of the recruitment of paraspeckle proteins. Using this system, we demonstrate that Men ɛ/β ncRNAs are essential to initiate the
de novo
assembly of paraspeckles. These newly formed structures effectively harbour nuclear-retained mRNAs confirming that they are
bona fide
functional paraspeckles. By three independent approaches, we show that it is the act of Men ɛ/β transcription, but not ncRNAs alone, that regulates paraspeckle maintenance. Finally, fluorescence recovery after photobleaching (FRAP) analyses supported a critical structural role for Men ɛ/β ncRNAs in paraspeckle organization. This study establishes a model in which Men ɛ/β ncRNAs serve as a platform to recruit proteins to assemble paraspeckles.
Journal Article
Gene bookmarking accelerates the kinetics of post-mitotic transcriptional re-activation
Although transmission of the gene expression program from mother to daughter cells has been suggested to be mediated by gene bookmarking, the precise mechanism by which bookmarking mediates post-mitotic transcriptional re-activation has been unclear. Here, we used a real-time gene expression system to quantitatively demonstrate that transcriptional activation of the same genetic locus occurs with a significantly more rapid kinetics in post-mitotic cells versus interphase cells. RNA polymerase II large subunit (Pol II) and bromodomain protein 4 (BRD4) were recruited to the locus in a different sequential order on interphase initiation versus post-mitotic re-activation resulting from the recognition by BRD4 of increased levels of histone H4 Lys 5 acetylation (H4K5ac) on the previously activated locus. BRD4 accelerated the dynamics of messenger RNA synthesis by de-compacting chromatin and hence facilitating transcriptional re-activation. Using a real-time quantitative approach, we identified differences in the kinetics of transcriptional activation between interphase and post-mitotic cells that are mediated by a chromatin-based epigenetic mechanism.
Spector and colleagues demonstrate that transcriptional activation after mitosis occurs with much faster kinetics than in interphase. Increased acetylation of lysine 5 on histone H4 is maintained during mitosis to recruit bromodomain protein 4, which then facilitates chromatin decompaction for transcriptional reactivation.
Journal Article
Allele-specific differential regulation of monoallelically expressed autosomal genes in the cardiac lineage
Each mammalian autosomal gene is represented by two alleles in diploid cells. To our knowledge, no insights have been made in regard to allele-specific regulatory mechanisms of autosomes. Here we use allele-specific single cell transcriptomic analysis to elucidate the establishment of monoallelic gene expression in the cardiac lineage. We find that monoallelically expressed autosomal genes in mESCs and mouse blastocyst cells are differentially regulated based on the genetic background of the parental alleles. However, the genetic background of the allele does not affect the establishment of monoallelic genes in differentiated cardiomyocytes. Additionally, we observe epigenetic differences between deterministic and random autosomal monoallelic genes. Moreover, we also find a greater contribution of the maternal versus paternal allele to the development and homeostasis of cardiac tissue and in cardiac health, highlighting the importance of maternal influence in male cardiac tissue homeostasis. Our findings emphasize the significance of allele-specific insights into gene regulation in development, homeostasis and disease.
The authors use allele-specific single cell transcriptomic analysis to elucidate the establishment of monoallelic gene expression in the cardiac lineage. The findings emphasize the importance of allele-specific insight into gene regulation in development, homeostasis and disease.
Journal Article
MaTAR25 lncRNA regulates the Tensin1 gene to impact breast cancer progression
Misregulation of long non-coding RNA (lncRNA) genes has been linked to a wide variety of cancer types. Here we report on
Mammary Tumor Associated RNA 25
(
MaTAR25
), a nuclear enriched and chromatin associated lncRNA that plays a role in mammary tumor cell proliferation, migration, and invasion, both in vitro and in vivo.
MaTAR25
functions by interacting with purine rich element binding protein B (PURB), and associating with a major downstream target gene
Tensin1
(
Tns1
) to regulate its expression in
trans
. The Tns1 protein product is a critical component of focal adhesions linking signaling between the extracellular matrix and the actin cytoskeleton. Knockout of
MaTAR25
results in down-regulation of
Tns1
leading to a reorganization of the actin cytoskeleton, and a reduction of focal adhesions and microvilli. We identify
LINC01271 as
the human ortholog of
MaTAR25
, and importantly, increased expression of
LINC01271
is associated with poor patient prognosis and metastasis. Our findings demonstrate that
LINC01271
represents a potential therapeutic target to alter breast cancer progression.
A group of long non-coding RNAs (lncRNAs),
Mammary Tumor Associated RNA
s
1-30
(
MaTARs
1-30
), are differentially expressed between mammary tumor cells and normal mammary epithelial cells. Here the authors report that
MaTAR25
plays a role in breast cancer cell proliferation, migration and invasion by regulating the expression of the
Tensin1
gene in
trans
.
Journal Article