Messenger RNA in Eukaryotes

Abstract

The concept that eukaryotic gene expression is primarily regulated at the level of RNA (ribonucleic acid) polymerase II recruitment to a promoter has changed dramatically during the past decades. Changes such as mRNA capping, splicing, polyadenylation, editing as well as various chemical modifications produce a huge variety of unique mRNA species. The mRNA factory model suggests that transcription and mRNA processing are intimately coupled. Thus, the elongating RNA polymerase II, via its carboxy‐terminal domain (CTD), recruits key factors required for the proper capping, splicing and polyadenylation to the nascent transcript. Furthermore, factors controlling the speed of elongation, such as nucleosome occupancy and modification, also partake in the generation of alternatively spliced mRNA, a process that represents an important regulatory level at which eukaryotes can expand the coding capacity of their genomes.

Key Concepts

  • mRNA processing events, such as capping, splicing and polyadenylation, are coordinated and occur predominantly co‐transcriptionally.
  • Different phosphorylation patterns of the carboxy‐terminal domain (CTD) control the temporal recruitment of capping, splicing and polyadenylation factors to the elongating RNA polymerase II.
  • Nucleosomes are preferentially found at exonic sequences and influence the speed of elongation and outcome of co‐transcriptional splicing.
  • Essentially, all eukaryotic genes produce alternatively spliced and polyadenylated mRNAs.
  • Alternative splicing greatly expands the coding capacity of a gene; that is one gene does not only code for one protein.
  • mRNA splicing, mRNA export and nonsense‐mediated mRNA decay are tightly coupled reactions that ensure that erroneous mRNAs are destroyed.
  • RNA editing is an important regulatory mechanism to produce protein diversity and control various aspects of the mRNA life cycle.
  • Dynamic ribonucleotide modifications, such as adenosine methylation, present a novel way to regulate mRNA stability, localisation and translation.

Keywords: RNA splicing; capping; polyadenylation; RNA editing; internal ribonucleotide modifications; coupling transcription RNA processing; carboxy‐terminal domain (CTD); RNA export; exon junction complex (EJC); transcription export complex (TREX)

Figure 1. Schematic overview of the structural alterations occurring on pre‐mRNA (messenger ribonucleic acid). Functional consequences of each described alteration (capping, splicing, polyadenylation, editing and internal covalent modifications) are indicated as the boxed text.
Figure 2. Coupling of RNA polymerase II transcription and RNA processing in higher eukaryotes. The carboxy‐terminal domain (CTD) recruits RNA processing factors to the transcribing RNA polymerase II. At the initiation phase of transcription the CTD is phosphorylated at Ser5 and binds factors required for capping of the nascent RNA chain. During the elongation phase, the CTD becomes phosphorylated at Ser2 and binds and deposits RNA splicing factors along the transcript and factors required for cleavage and polyadenylation of the nascent transcript. Nucleosomes are preferentially positioned at exonic sequences and cause a slow‐down of RNA polymerase II elongation. Additional splicing factors, which associate with nucleosomes carrying specific histone H3 methylation marks (labelled with star), can regulate co‐transcriptional splicing. Intron sequences are shown as black lines and protein‐coding exon sequences shown as red lines. TSS denotes transcriptional start site.
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Further Reading

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How to Cite close
Akusjärvi, Göran, and Punga, Tanel(Dec 2017) Messenger RNA in Eukaryotes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000875.pub3]