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. 2011:2011:626081.
doi: 10.4061/2011/626081. Epub 2011 Nov 24.

Spatial Organization and Dynamics of Transcription Elongation and Pre-mRNA Processing in Live Cells

Miguel Sánchez-Álvarez  1 , Noemí Sánchez-Hernández, Carlos Suñé
Affiliations

Spatial Organization and Dynamics of Transcription Elongation and Pre-mRNA Processing in Live Cells

Miguel Sánchez-Álvarez et al. Genet Res Int. 2011.

Abstract

During the last 30 years, systematic biochemical and functional studies have significantly expanded our knowledge of the transcriptional molecular components and the pre-mRNA processing machinery of the cell. However, our current understanding of how these functions take place spatiotemporally within the highly compartmentalized eukaryotic nucleus remains limited. Moreover, it is increasingly clear that "the whole is more than the sum of its parts" and that an understanding of the dynamic coregulation of genes is essential for fully characterizing complex biological phenomena and underlying diseases. Recent technological advances in light microscopy in addition to novel cell and molecular biology approaches have led to the development of new tools, which are being used to address these questions and may contribute to achieving an integrated and global understanding of how the genome works at a cellular level. Here, we review major hallmarks and novel insights in RNA polymerase II activity and pre-mRNA processing in the context of nuclear organization, as well as new concepts and challenges arising from our ability to gather extensive dynamic information at the single-cell resolution.

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Figures

Figure 1
Figure 1
Model of the basic structure and function of RNAPII transcription factories. (a) A “gene-loop” is recruited upon activation to the transcription factory, which contains immobilized subunits of RNAPII. (b) The gene-loop is then “reeled” onto RNAPII for transcriptional elongation. (c) Upon termination, the anchoring of the locus allows for subsequent rounds of transcription. Adapted, with permission, from The Journal of Cell Science [47].
Figure 2
Figure 2
Three potential, nonexclusive models for the role of the interchromatin granule clusters (IGCs) in the regulation of transcription and pre-mRNA processing machinery. IGCs are depicted surrounded by transcriptionally competent sites or “factories” (grey beads). (a) IGCs may be specialized sites for the recycling and assembly of transcription (dark and light red beads) and pre-mRNA processing complexes (dark and light green beads) through regulated posttranslational modification cycles. Dark and light hue code denotes active and inactive pools of factors, respectively. (b) Posttranscriptional processing steps and potential surveillance of mRNA quality may be integrated in these structures, constituting a “checkpoint link” between mRNA transcription and mRNP assembly and export. A given transcript may include both introns that are spliced cotranscriptionally outside of the IGCs (orange lariat) and intron sequences that are processed posttranscriptionally (dark brown stretch and lariat). The later event may be also coupled in the IGCs to surveillance mechanisms, mRNP assembly (blue beads), and export. (c) Specific subsets of nuclear factors, such as ncRNAs (MALAT1, 7SK; see main text; depicted in the lower panel as thin blue threads), can function as active quenchers or sequesters of transcription and pre-mRNA processing factors (red and green beads, resp.), blocking the recruitment of these complexes from the IGCs to nearby active sites of transcription.
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