Non-coding RNAs: hope or hype?

Hüttenhofer, Alexander; Schattner, Peter; Polacek, Norbert

doi:10.1016/j.tig.2005.03.007

Cited by 376 publications

(264 citation statements)

References 80 publications

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“…To our knowledge, this is the first attempt of this kind and the study would not be complete without addressing the heavily discussed question on the number of functional RNAs in the human genome 8 . The history of protein gene finding, however, demonstrates the problems of estimating gene numbers 33 .…”

Section: Discussionmentioning

confidence: 99%

Mapping of conserved RNA secondary structures predicts thousands of functional noncoding RNAs in the human genome

et al. 2005

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In contrast to the fairly reliable and complete annotation of the protein coding genes in the human genome, comparable information is lacking for non-coding RNAs. We present a comparative screen of vertebrate genomes for structural non-coding RNAs, which evaluates sequence conservation, secondary structure conservation, and thermodynamic stability of putative RNA structures. We predict more than 30 000 structured RNA elements in the human genome, almost 1000 of which are conserved across all vertebrates. Roughly a third is found in introns of known genes, a sixth are potential regulatory elements in untranslated regions, about half are located far away of any known gene. Only a small fraction of these sequences has been described previously. EST data demonstrate, however, that the majority of them is at least transcribed. The widespread conservation of secondary structure points to a large number of functional ncRNAs in the human genome, which we estimate to be comparable to the number of protein-coding genes. The recent finishing of the human genome sequence emphasizes the "need for reliable experimental and computational methods for comprehensive identification of non-coding RNAs" 1 . A variety of experimental techniques have been used to uncover the human and mouse transcriptomes, in particular tiling arrays 2-4 , cDNA sequencing 5,6 , and unbiased mapping of transcription factor binding sites 7 . All these studies agree that a substantial fraction of the genome is transcribed and that a large fraction of the transcriptome consists of non-coding RNAs. It is unclear, however, which fraction are functional non-coding RNAs (ncRNAs), and which constitutes "transcriptional noise" 8 .Genome-wide computational surveys of ncRNAs, on the other hand, have been impossible until recently, because ncRNAs do not share common signals that could be detected at the sequence level. A large class of ncRNAs, however, has characteristic structures that are functional and hence are well conserved over evolutionary timescales: most of the "classical" ncRNAs, including rRNAs, tRNAs, snRNAs, snoRNAs, as well as the RNA components of RNAse P and the signal recognition particle, are of this type. The stabilizing selection acting on the secondary structure causes characteristic substitution patterns in the underlying sequences: Consistent and compensatory mutations replace one type of base-pair by another one in the paired regions (helices) of the molecule. In addition, loop regions are more variable than helices. These patterns can be ex-1 ploited in comparative computational approaches 9-12 to discriminate functional RNAs from other types of conserved sequence. Recently, high levels of sequence conservation of non-coding DNA regions have been reported 13, 14 . Here we screen the complete collection of conserved non-coding DNA sequences from mammalian genomes and provide a first annotation of the complement of structurally conserved RNAs in the human genome. ResultsSelection of conserved sequences and screening for structural RNAs We s...

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Section: Discussionmentioning

confidence: 99%

Mapping of conserved RNA secondary structures predicts thousands of functional noncoding RNAs in the human genome

et al. 2005

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“…Dnmt1 has been previously shown to undergo transcriptional regulation by the expression of truncated proteins in other species (Aniello et al, 2003). Moreover, the transcription of untranslated mRNAs has been recently suggested to comprise an important form of gene expression regulation (Huttenhofer et al, 2005), suggesting that Dnmt1b may have a significant physiological function regardless of its translation into a functional or truncated protein.…”

Section: Discussionmentioning

confidence: 99%

Alternative splicing and expression analysis of bovine DNA methyltransferase 1

Russell

Betts

2008

Developmental Dynamics

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Methylation of specific CG residues in the mammalian genome results in tissue-specific patterns of gene expression, which are critical for cell differentiation. Embryos that fail to establish and maintain proper DNA methylation patterns show severe developmental abnormalities as is the case of DNA methyltransferase 1 (Dnmt1) -deficient embryos. Dnmt1 is the main maintenance methyltransferase in the mouse and its expression is regulated by a splicing mechanism that dictates the expression of stage-specific isoforms. Little is known about Dnmt1 expression in the cow and isoforms of Dnmt1 are yet unknown in this species. Here we demonstrate that the previously described bovine Dnmt1 transcript is ubiquitously expressed in embryos and fetal tissue. In addition, we report the identification of a splice variant of the bovine Dnmt1, which shows a ubiquitous expression pattern. This new transcript was detected using 5 RACE and genomic mapping and its expression pattern was shown to be consistent with a tissue-specific mode of regulation. Furthermore, our analysis shows that the expression of an oocyte-specific isoform of Dnmt1 is unlikely to occur in cattle. The newly reported isoform of Dnmt1 was demonstrated to be, similarly to Dnmt1a, polyadenylated and if translated possess the functional domains necessary for maintenance and de novo methyltransferase activity.

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“…Recent discoveries involving a variety of new ncRNA genes [85], biological roles and action mechanisms have shown that the diversity and importance of ncRNAs were underestimated [65]. Nowadays, it is known that functional RNAs that do not code to proteins perform important roles.…”

Section: Introductionmentioning

confidence: 99%

“…New long antisense ncRNAs have been found in many genomes, that seem to be involved in gene expression regulation [65,98,113,114]. In addition, many more ncRNAs are expected to be unveiled [37,65].…”

Section: Introductionmentioning

confidence: 99%

Computational methods in noncoding RNA research

2007

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Non protein-coding RNAs (ncRNAs) are a research hotspot in bioinformatics. Recent discoveries have revealed new ncRNA families performing a variety of roles, from gene expression regulation to catalytic activities. It is also believed that other families are still to be unveiled. Computational methods developed for protein coding genes often fail when searching for ncRNAs. Noncoding RNAs functionality is often heavily dependent on their secondary structure, which makes gene discovery very different from protein coding RNA genes. This motivated the development of specific methods for ncRNA research. This article reviews the main approaches used to identify ncRNAs and predict secondary structure.

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Non-coding RNAs: hope or hype?

Cited by 376 publications

References 80 publications

Mapping of conserved RNA secondary structures predicts thousands of functional noncoding RNAs in the human genome

Mapping of conserved RNA secondary structures predicts thousands of functional noncoding RNAs in the human genome

Alternative splicing and expression analysis of bovine DNA methyltransferase 1

Computational methods in noncoding RNA research

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