title: Alternative mRNA transcription, processing, and translation: insights from RNA sequencing.
abstract: The human transcriptome comprises >80,000 protein-coding transcripts and the estimated number of proteins synthesized from these transcripts is in the range of 250,000 to 1 million. These transcripts and proteins are encoded by less than 20,000 genes, suggesting extensive regulation at the transcriptional, post-transcriptional, and translational level. Here we review how RNA sequencing (RNA-seq) technologies have increased our understanding of the mechanisms that give rise to alternative transcripts and their alternative translation. We highlight four different regulatory processes: alternative transcription initiation, alternative splicing, alternative polyadenylation, and alternative translation initiation. We discuss their transcriptome-wide distribution, their impact on protein expression, their biological relevance, and the possible molecular mechanisms leading to their alternative regulation. We conclude with a discussion of the coordination and the interdependence of these four regulatory layers.
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Eleonora
authors: E
authors: de Klerk
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: p.a.c.hoen@lumc.nl.
authors: Peter A C
authors: PA
authors: 't Hoen
mesh_terms: D017398:Alternative Splicing; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D026723:Polyadenylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics*; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D012333:RNA, Messenger
keywords: RNA sequencing; alternative polyadenylation; alternative splicing; gene expression; transcriptome; translation