Genome-wide transcription and the implications for genomic organization

Abstract

Recent evidence of genome-wide transcription in several species indicates that the amount of transcription that occurs cannot be entirely accounted for by current sets of genome-wide annotations. Evidence indicates that most of both strands of the human genome might be transcribed, implying extensive overlap of transcriptional units and regulatory elements. These observations suggest that genomic architecture is not colinear, but is instead interleaved and modular, and that the same genomic sequences are multifunctional: that is, used for multiple independently regulated transcripts and as regulatory regions. What are the implications and consequences of such an interleaved genomic architecture in terms of increased information content, transcriptional complexity, evolution and disease states?

Validation of predicted mRNA splicing mutations using high-throughput transcriptome data

“…As sequencing technologies improve, the proportion of validated mutations is expected to increase. Such an increase would mirror that observed for the prevalence of alternative splicing events 34 . It is important to note that acceptance of the null hypothesis, due to an absence of evidence required to disprove it, does not imply that the underlying prediction of a mutation at a particular locus is incorrect, but merely that the current empirical methods employed were insufficient to corroborate it.…”

“…In fact, evidence indicates that a significant portion of the genome is transcribed 34 , and it is estimated that 95% of known genes are alternatively spliced 30 . Defective mRNA splicing can lead to multiple alternative transcripts including those with retained introns, cassette exons, alternate promoters/terminators, extended or truncated exons, and reduced exons 35 .…”

Transcription termination by nuclear RNA polymerases

“…However, West et al (2006a) showed that the 59 products of b-globin transcription resulting from cleavage at the CoTC frequently contain a short A-tail and accumulate upon siRNAmediated depletion of the Rrp6 human homolog. But more importantly, new noncoding RNAs with unknown function were recently detected in the human genome (Kapranov et al 2007). Further studies will be needed to elucidate the role of these RNAs and to reveal whether or not they function in gene expression.…”

“…CUTs provide an example of RNAs controlled by the Nrd1 complex that appear important for regulation of mRNA expression. Despite the existence of human homologs of exosome and TRAMP subunits, there is still only limited evidence for such an RNA quality and gene expression control pathway in humans Kapranov et al 2007;Vanacova and Stefl 2007). However, West et al (2006a) showed that the 59 products of b-globin transcription resulting from cleavage at the CoTC frequently contain a short A-tail and accumulate upon siRNAmediated depletion of the Rrp6 human homolog.…”

Noncoding RNAs: Different roles in tumorigenesis

“…In this review, we focus on the current status of several classes of ncRNAs associated with cancer with the emphasis on those that are not microRNAs. Mounting evidence has revealed that a major portion of the mammalian genome is transcribed to produce large numbers of noncoding RNAs (ncRNAs), that is, RNAs that either do not have an open reading frame or RNAs that have a short poorly conserved open reading frame and do not code for a protein [1,2]. During the past decade, the discovery of small RNAs including the microRNAs (miRNAs) and small interfering RNAs (siRNAs) has led to major advances in biology.…”