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Review
. 2017 Jun 3;14(6):761-778.
doi: 10.1080/15476286.2016.1243649. Epub 2016 Oct 7.

Towards an understanding of regulating Cajal body activity by protein modification

Michael D Hebert  1 , Aaron R Poole  1
Affiliations
Review

Towards an understanding of regulating Cajal body activity by protein modification

Michael D Hebert et al. RNA Biol. .

Abstract

The biogenesis of small nuclear ribonucleoproteins (snRNPs), small Cajal body-specific RNPs (scaRNPs), small nucleolar RNPs (snoRNPs) and the telomerase RNP involves Cajal bodies (CBs). Although many components enriched in the CB contain post-translational modifications (PTMs), little is known about how these modifications impact individual protein function within the CB and, in concert with other modified factors, collectively regulate CB activity. Since all components of the CB also reside in other cellular locations, it is also important that we understand how PTMs affect the subcellular localization of CB components. In this review, we explore the current knowledge of PTMs on the activity of proteins known to enrich in CBs in an effort to highlight current progress as well as illuminate paths for future investigation.

Keywords: Cajal body; SMN; WRAP53; coilin; phosphorylation; post-translational modification; telomerase.

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Figures

Figure 1.
Figure 1.
PTMs and snRNP biogenesis. A model showing known modifications of proteins involved in snRNP biogenesis, including the snRNA export pathway. Enzymes that modify these proteins are shown. Phosphorylated, methylated, ubiquitinated and sumoylated proteins are indicated. Processes marked by question marks indicate that there is no information on how PTMs affect localization or interaction; or where the PTM is known, but the enzyme(s) responsible for the modification are not known. Proteins that are modified, such as TGS1, but the functional consequence of this modification and the modifying enzymes are unknown, are indicated in the figure but lack denoted modification. Also not shown in the model are proteins with combinations of PTMs. (P = Phosphorylation; Me = Methylation; So = Sumoylation; Ub = Ubiquitination).
Figure 2.
Figure 2.
Modifications and modifiers of coilin, the CB marker protein. Enzymes known to modify coilin are shown. Not shown are coilin proteins with multiple different PTMs. During mitosis, coilin is hyperphosphorylated (coilin with 6 phosphorylations), which correlates with decreased coilin self-association and disassembled CBs. Hypomethylated coilin, which is enriched within the nucleolus, is indicated. Also shown in the nucleolus is a coilin phosphomutant (S184A). More details in text.
Figure 3.
Figure 3.
The impact of PTMs on the interactions and localizations of SMN and coilin. It is hypothesized that coilin in the nucleoplasm is hyperphosphorylated compared to coilin in CBs. During mitosis, coilin is hyperphosphorylated and CBs disassemble. CBs reform early to mid G1 (indicated in model). Mitotic coilin is reduced in its self-association compared to interphase coilin (paired coilin in the CB). Coilin interacts with SMN, Sm proteins, sRNPs and WRAP53. Methylation of coilin (and certain SM proteins) increases it interaction with SMN. Phosphorylation of coilin differentially affects its interaction with SMN and Sm proteins, with SMN preferentially binding to coilin that is less phosphorylated than that preferred by Sm proteins. The differential interaction of coilin with SMN and Sm proteins may disengage the nascent snRNP from the SMN complex in the CB, allowing for subsequent snRNP biogenesis steps, including snRNA modification and snRNP-specific protein association. Many non-coding RNAs, such as scaRNAs, snRNAs and snoRNAs are enriched in the CB and coilin complex (curved lines). Coilin interaction with RNAs decreases when coilin is hyperphosphorylated.
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