The Fragmented Gene

Brosius, Jürgen

doi:10.1111/j.1749-6632.2009.05004.x

Cited by 23 publications

(24 citation statements)

References 62 publications

(96 reference statements)

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“…The first comprises all protein coding messenger RNAs (mRNAs), and various subclasses of non-protein coding RNAs constitute the second (1,2). Although non-protein coding RNAs do not encode proteins, they are key players in controlling diverse biochemical pathways.…”

Section: Introductionmentioning

confidence: 99%

“…Although non-protein coding RNAs do not encode proteins, they are key players in controlling diverse biochemical pathways. Functions carried out by non-protein coding RNAs might be exerted by the RNA itself or in complex with proteins (1–3). RNA size criteria to define small non-protein coding RNA (The size cutoff for defining small RNAs used to be about 500 nt to include small RNAs, such as SRP RNA (300 nt), 7SK RNA (332 nt), MRP RNA (287 nt) and small nuclear RNAs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Biases in small RNA deep sequencing data

Raabe¹,

Tang²,

Brosius³

et al. 2013

Nucleic Acids Research

183

177

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High-throughput RNA sequencing (RNA-seq) is considered a powerful tool for novel gene discovery and fine-tuned transcriptional profiling. The digital nature of RNA-seq is also believed to simplify meta-analysis and to reduce background noise associated with hybridization-based approaches. The development of multiplex sequencing enables efficient and economic parallel analysis of gene expression. In addition, RNA-seq is of particular value when low RNA expression or modest changes between samples are monitored. However, recent data uncovered severe bias in the sequencing of small non-protein coding RNA (small RNA-seq or sRNA-seq), such that the expression levels of some RNAs appeared to be artificially enhanced and others diminished or even undetectable. The use of different adapters and barcodes during ligation as well as complex RNA structures and modifications drastically influence cDNA synthesis efficacies and exemplify sources of bias in deep sequencing. In addition, variable specific RNA G/C-content is associated with unequal polymerase chain reaction amplification efficiencies. Given the central importance of RNA-seq to molecular biology and personalized medicine, we review recent findings that challenge small non-protein coding RNA-seq data and suggest approaches and precautions to overcome or minimize bias.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biases in small RNA deep sequencing data

Raabe¹,

Tang²,

Brosius³

et al. 2013

Nucleic Acids Research

183

177

View full text Add to dashboard Cite

show abstract

“…In any event, it is much more common that novel gene modules are being added to existing genes. Such co-opted or exapted modules can be derived from inter-or intragenic space and constitute novel protein-coding exons and regulatory regions such as promoters and enhancers (Brosius 2005b(Brosius , 2009Baertsch et al 2008;Rebollo et al 2012). 5 A prominent case is the exonization of parts of Alu elements, usually as alternatively spliced exons (Makalowski et al 1994;Nekrutenko and Li 2001;Sorek et al 2002;Lev-Maor et al 2003;Krull et al 2005;Shen et al 2011).…”

Section: Yesterday's Junk Could Become Tomorrow's Novel Gene Module mentioning

confidence: 99%

The Persistent Contributions of RNA to Eukaryotic Gen(om)e Architecture and Cellular Function

Brosius

2014

Cold Spring Harbor Perspectives in Biology

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“…Conversely, the term gene itself and the modular architecture of genes and genomes could be defined by TSSs and PASs (1). Indeed, in certain extreme cases, ribonucleic acids (RNAs) are transcribed from components that overlap two genes; thus, the definitions of genes are not always straightforward (2).…”

Section: Introductionmentioning

confidence: 99%

Construction of mate pair full-length cDNAs libraries and characterization of transcriptional start sites and termination sites

Matsumoto

Suzuki

Wakaguri

et al. 2014

Nucleic Acids Research

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To identify and characterize transcript structures ranging from transcriptional start sites (TSSs) to poly(A)-addition sites (PASs), we constructed and analyzed human TSS/PAS mate pair full-length cDNA libraries from 14 tissue types and four cell lines. The collected information enabled us to define TSS cluster (TSC) and PAS cluster (PAC) relationships for a total of 8530/9400 RefSeq genes, as well as 4251/5618 of their putative alternative promoters/terminators and 4619/4605 intervening transcripts, respectively. Analyses of the putative alternative TSCs and alternative PACs revealed that their selection appeared to be mostly independent, with rare exceptions. In those exceptional cases, pairs of transcript units rarely overlapped one another and were occasionally separated by Rad21/CTCF. We also identified a total of 172 similar cases in which TSCs and PACs spanned adjacent but distinct genes. In these cases, different transcripts may utilize different functional units of a particular gene or of adjacent genes. This approach was also useful for identifying fusion gene transcripts in cancerous cells. Furthermore, we could construct cDNA libraries in which 3′-end mate pairs were distributed randomly over the transcripts. These libraries were useful for assembling the internal structure of previously uncharacterized alternative promoter products, as well as intervening transcripts.

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The Fragmented Gene

Cited by 23 publications

References 62 publications

Biases in small RNA deep sequencing data

Biases in small RNA deep sequencing data

The Persistent Contributions of RNA to Eukaryotic Gen(om)e Architecture and Cellular Function

Construction of mate pair full-length cDNAs libraries and characterization of transcriptional start sites and termination sites

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