Genomics: The amazing complexity of the human transcriptome

Frith, Martin C.; Pheasant, Michael; Mattick, John S.

doi:10.1038/sj.ejhg.5201459

Cited by 180 publications

(132 citation statements)

References 19 publications

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“…6,7 According to their transcript size, ncRNAs are grouped into two major classes: (i) small ncRNAs with transcripts o200 nucleotides (nt; eg, aforementioned siRNAs and miRNAs, Piwi-interacting RNAs, and some retrotransposon-derived RNAs) and (ii) long non-coding RNAs (lncRNAs), this class includes five broad categories: sense, antisense, bidirectional, intronic, and intergenic, based on the proximity between neighboring transcripts. 8 For a time, lncRNAs was commonly defined as a proteincoding transcripts that is 4200 nt. 9 However, this definition is arbitrary and limits in distinguishing lncRNAs from small regulatory ncRNAs, without taking its distinct structure or function characteristics into account.…”

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confidence: 99%

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Pan

2014

Modern Pathology

102

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Long non-coding RNAs (lncRNAs) are a class of newly identified non-coding RNA molecules that are emerging as key regulators of tumor initiation and development. Colorectal cancer (CRC) remains a major health problem worldwide, and there remains a need to further refine the current screening approaches as well as provide tailored diagnostic and therapeutic approaches. Multiple dysregulated lncRNAs participate in tumorigenesis through a variety of molecular mechanisms, and various regulatory factors frequently contribute to the aberrant expression of lncRNAs in CRC, thereby allowing malignant transformation. Additionally, the association of dysregulated lncRNAs with specific developmental stages and clinical outcomes indicates their potential as strong diagnostic and prognostic predictors as well as therapeutic targets. Here we provide a brief overview of the known functions of CRC-associated lncRNAs, describe some potential molecular mechanisms that underlie changes in lncRNA expression in CRC, and attempt to uncover their clinical and therapeutic potential. Keywords: colorectal cancer; diagnosis; dysregulation; long non-coding RNA; prognosis High-throughput genome-scale studies have demonstrated that more than 93% of the DNA sequences in the human genome are actively transcribed. 1 However, only approximately 5-10% of the sequences are stably transcribed into mRNA or non-coding RNA (ncRNA). Genome tiling arrays have revealed that the amount of non-coding sequence is at least four times larger than the amount of coding sequence, which indicates that only 1% of the human genome is composed of protein-coding genes and the remaining 4-9% is transcribed into ncRNAs. 2 Therefore, ncRNAs constitute a very large proportion of the total RNA molecules.The function and clinical significance of short regulatory ncRNAs, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), were elucidated first, 3 and the regulatory roles of miRNAs have been broadly recognized in almost all physiological and pathological processes in the body, including carcinogenesis. 4 For example, we previously reported that MIR95 promotes cell proliferation and targets sorting nexin 1 in human colorectal carcinoma; 5 moreover, in colorectal cancer (CRC) patients, the plasma levels of MIR29a and MIR92a are significantly upregulated and the plasma levels of MIR601 and MIR760 are significantly downregulated; thus the levels of these miRNAs have good diagnostic value for CRC screening. 6,7 According to their transcript size, ncRNAs are grouped into two major classes: (i) small ncRNAs with transcripts o200 nucleotides (nt; eg, aforementioned siRNAs and miRNAs, Piwi-interacting RNAs, and some retrotransposon-derived RNAs) and (ii) long non-coding RNAs (lncRNAs), this class includes five broad categories: sense, antisense, bidirectional, intronic, and intergenic, based on the proximity between neighboring transcripts. 8 For a time, lncRNAs was commonly defined as a proteincoding transcripts that is 4200 nt. 9 However, this definition is arbitrary and ...

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confidence: 99%

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Pan

2014

Modern Pathology

102

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“…The percentage of the transcribed noncoding sequences in mice and human genomes exceed 90% (1), and the functional importance of the rest of the noncoding RNA is now only beginning to be understood (2). The noncoding roles of ribosomal RNA (rRNA) and transfer RNA (tRNA) are well known, but the discovery of ribozymes (RNA enzymes) has sparked an intense search for the functional roles of the rest of the noncoding RNA molecules (2,3), which include catalysis, replication, transcriptional and translational regulation, and ligand binding (4), just to name a few.…”

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confidence: 99%

Assembly mechanisms of RNA pseudoknots are determined by the stabilities of constituent secondary structures

Cho

Pincus

Thirumalai

2009

Proc. Natl. Acad. Sci. U.S.A.

107

156

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Understanding how RNA molecules navigate their rugged folding landscapes holds the key to describing their roles in a variety of cellular functions. To dissect RNA folding at the molecular level, we performed simulations of three pseudoknots (MMTV and SRV-1 from viral genomes and the hTR pseudoknot from human telomerase) using coarse-grained models. The melting temperatures from the specific heat profiles are in good agreement with the available experimental data for MMTV and hTR. The equilibrium free energy profiles, which predict the structural transitions that occur at each melting temperature, are used to propose that the relative stabilities of the isolated helices control their folding mechanisms. Kinetic simulations, which corroborate the inferences drawn from the free energy profiles, show that MMTV folds by a hierarchical mechanism with parallel paths, i.e., formation of one of the helices nucleates the assembly of the rest of the structure. The SRV-1 pseudoknot, which folds in a highly cooperative manner, assembles in a single step in which the preformed helices coalesce nearly simultaneously to form the tertiary structure. Folding occurs by multiple pathways in the hTR pseudoknot, the isolated structural elements of which have similar stabilities. In one of the paths, tertiary interactions are established before the formation of the secondary structures. Our work shows that there are significant sequence-dependent variations in the folding landscapes of RNA molecules with similar fold. We also establish that assembly mechanisms can be predicted using the stabilities of the isolated secondary structures.kinetic partitioning mechanism ͉ parallel pathways ͉ ribosomal frameshifting ͉ RNA folding T he RNA folding problem has taken center stage in molecular biology because these molecules play a vital role in a variety of cellular functions. The percentage of the transcribed noncoding sequences in mice and human genomes exceed 90% (1), and the functional importance of the rest of the noncoding RNA is now only beginning to be understood (2). The noncoding roles of ribosomal RNA (rRNA) and transfer RNA (tRNA) are well known, but the discovery of ribozymes (RNA enzymes) has sparked an intense search for the functional roles of the rest of the noncoding RNA molecules (2, 3), which include catalysis, replication, transcriptional and translational regulation, and ligand binding (4), just to name a few. Consequently, it is important to determine the mechanisms by which RNA molecules fold so that a deeper understanding of the structure-function relationship can emerge.Although great progress has been made in understanding of how RNA molecules fold (5Ϫ10) global principles that determine the sequence dependent folding mechanisms have not fully emerged. It is argued that RNA folding mechanisms must be inherently simple because of the apparent separation in the energy scales that describe the different levels of structural organization (11). Furthermore, RNA molecules are constructed from only four nucleotides (nts), ...

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“…To these figures, we have to add alternative splicing of protein-coding RNAs, small and non-coding RNAs (ncRNA) (approximately 16,000 in mice), and several different types of antisense RNA. Such RNA variants make up about three quarters of a transcriptionally active mammalian genome (Frith et al 2005;Suzuki and Hayashizaki 2004). It is thus evident that the genomic resources currently available for flatfishes are still too scarce to gather a profound knowledge of the biology of these species, and therefore they should be augmented.…”

Section: Flatfish Genomics Researchmentioning

confidence: 99%

Advances in genomics for flatfish aquaculture

Cerdà

Manchado

2012

Genes Nutr

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Fish aquaculture is considered to be one of the most sustainable sources of protein for humans. Many different species are cultured worldwide, but among them, marine flatfishes comprise a group of teleosts of high commercial interest because of their highly prized white flesh. However, the aquaculture of these fishes is seriously hampered by the scarce knowledge on their biology. In recent years, various experimental 'omics' approaches have been applied to farmed flatfishes to increment the genomic resources available. These tools are beginning to identify genetic markers associated with traits of commercial interest, and to unravel the molecular basis of different physiological processes. This article summarizes recent advances in flatfish genomics research in Europe. We focus on the new generation sequencing technologies, which can produce a massive amount of DNA sequencing data, and discuss their potentials and applications for de novo genome sequencing and transcriptome analysis. The relevance of these methods in nutrigenomics and foodomics approaches for the production of healthy animals, as well as high quality and safety products for the consumer, is also briefly discussed.

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Genomics: The amazing complexity of the human transcriptome

Cited by 180 publications

References 19 publications

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Assembly mechanisms of RNA pseudoknots are determined by the stabilities of constituent secondary structures

Advances in genomics for flatfish aquaculture

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