Synergistic interactions between Cajal bodies and the miRNA processing machinery

Our results demonstrate that Cajal bodies and the microRNA (miRNA) processing machinery functionally interact and together contribute to the biogenesis of miRNAs and small nuclear ribonucleoproteins.

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RNA-mediated interaction of Cajal bodies and U2 snRNA genes

The Journal of Cell Biology ◽

10.1083/jcb.200105084 ◽

2001 ◽

Vol 154 (3) ◽

pp. 499-510 ◽

Cited By ~ 73

Author(s):

Mark R. Frey ◽

A. Gregory Matera

Keyword(s):

Nuclear Export ◽

Marked Decrease ◽

Gene Clusters ◽

Cajal Bodies ◽

U2 Snrna ◽

Intragenic Deletions ◽

High Concentrations ◽

Nuclear Structures ◽

Insight Into ◽

Small Nuclear Ribonucleoproteins

Cajal bodies (CBs) are nuclear structures involved in RNA metabolism that accumulate high concentrations of small nuclear ribonucleoproteins (snRNPs). Notably, CBs preferentially associate with specific genomic loci in interphase human cells, including several snRNA and histone gene clusters. To uncover functional elements involved in the interaction of genes and CBs, we analyzed the expression and subcellular localization of stably transfected artificial arrays of U2 snRNA genes. Although promoter substitution arrays colocalized with CBs, constructs containing intragenic deletions did not. Additional experiments identified factors within CBs that are important for association with the native U2 genes. Inhibition of nuclear export or targeted degradation of U2 snRNPs caused a marked decrease in the levels of U2 snRNA in CBs and strongly disrupted the interaction with U2 genes. Together, the results illustrate a specific requirement for both the snRNA transcripts as well as the presence of snRNPs (or snRNP proteins) within CBs. Our data thus provide significant insight into the mechanism of CB interaction with snRNA loci, strengthening the putative role for this nuclear suborganelle in snRNP biogenesis.

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Subcellular localization of protein kinase C δ and ε affects transcriptional and post-transcriptional processes in four-cell mouse embryos

Reproduction ◽

10.1530/rep.1.00572 ◽

2005 ◽

Vol 130 (4) ◽

pp. 453-465 ◽

Cited By ~ 8

Author(s):

Hesam Dehghani ◽

Cara Reith ◽

Ann C Hahnel

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Subcellular Localization ◽

Cajal Bodies ◽

Message Processing ◽

Mrna Transcription ◽

Cell Stage ◽

Kinase C ◽

Sm Protein ◽

Small Nuclear Ribonucleoproteins

During mouse preimplantation development, two isozymes of protein kinase C (PKC), δ and ε, transiently localize to nuclei at the early four-cell stage. In order to study their functions at this stage, we altered the subcellular localization of these isozymes (ratio of nuclear to cytoplasmic concentrations) with peptides that specifically activate or inhibit translocation of each isozyme. The effects of altering nuclear concentration of each isozyme on transcription (5-bromouridine 5′-triphosphate (BrUTP) incorporation), amount and distribution of small nuclear ribonucleoproteins (snRNPs), nucleolar dynamics (immunocytochemistry for Smith antigen (Sm) protein) and the activity of embryonic alkaline phosphatase (EAP; histochemistry) were examined. We found that nuclear concentration of PKC ε correlated with total mRNA transcription. Higher nuclear concentrations of both PKC δ and ε decreased storage of snRNPs in Cajal bodies and decreased the number of nucleoli, but did not affect the nucleoplasmic concentration of snRNPs. Inhibiting translocation of PKC δ out of the nucleus at the early four-cell stage decreased cytoplasmic EAP activity, whereas inhibiting translocation of PKC ε increased EAP activity slightly. These results indicate that translocation of PKC δ and ε in and out of nuclei at the early four-cell stage in mice can affect transcription or message processing, and that sequestration of these PKC in nuclei can also affect the activity of a cytoplasmic protein (EAP).

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siRNA and miRNA processing: new functions for Cajal bodies

Current Opinion in Genetics & Development ◽

10.1016/j.gde.2008.01.008 ◽

2008 ◽

Vol 18 (2) ◽

pp. 197-203 ◽

Cited By ~ 76

Author(s):

Olga Pontes ◽

Craig S Pikaard

Keyword(s):

Cajal Bodies ◽

Mirna Processing

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Characterization of miRNA processing machinery in the embryonic chick lung

Cell and Tissue Research ◽

10.1007/s00441-015-2240-6 ◽

2015 ◽

Vol 362 (3) ◽

pp. 569-575 ◽

Cited By ~ 5

Author(s):

Rute Silva Moura ◽

Patrícia Vaz-Cunha ◽

Carla Silva-Gonçalves ◽

Jorge Correia-Pinto

Keyword(s):

Embryonic Chick ◽

Mirna Processing ◽

Processing Machinery

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Hyperglycemia increases microRNAs in circulating HDL from acute coronary syndrome patients and modulates miRNA processing machinery in human macrophages

Atherosclerosis ◽

10.1016/j.atherosclerosis.2016.07.504 ◽

2016 ◽

Vol 252 ◽

pp. e82

Author(s):

L.S. Niculescu ◽

N. Simionescu ◽

G.M. Sanda ◽

M.G. Carnuta ◽

C.S. Stancu ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Human Macrophages ◽

Mirna Processing ◽

Coronary Syndrome ◽

Processing Machinery

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Ongoing U snRNP Biogenesis Is Required for the Integrity of Cajal Bodies

Molecular Biology of the Cell ◽

10.1091/mbc.e06-03-0247 ◽

2006 ◽

Vol 17 (7) ◽

pp. 3221-3231 ◽

Cited By ~ 123

Author(s):

Ira Lemm ◽

Cyrille Girard ◽

Andreas N. Kuhn ◽

Nicholas J. Watkins ◽

Marc Schneider ◽

...

Keyword(s):

Modular Structure ◽

Cajal Bodies ◽

Marker Protein ◽

Detectable Concentration ◽

Nuclear Phase ◽

Nuclear Foci ◽

Small Nuclear Ribonucleoproteins ◽

In Cells

Cajal bodies (CBs) have been implicated in the nuclear phase of the biogenesis of spliceosomal U small nuclear ribonucleoproteins (U snRNPs). Here, we have investigated the distribution of the CB marker protein coilin, U snRNPs, and proteins present in C/D box small nucleolar (sno)RNPs in cells depleted of hTGS1, SMN, or PHAX. Knockdown of any of these three proteins by RNAi interferes with U snRNP maturation before the reentry of U snRNA Sm cores into the nucleus. Strikingly, CBs are lost in the absence of hTGS1, SMN, or PHAX and coilin is dispersed in the nucleoplasm into numerous small foci. This indicates that the integrity of canonical CBs is dependent on ongoing U snRNP biogenesis. Spliceosomal U snRNPs show no detectable concentration in nuclear foci and do not colocalize with coilin in cells lacking hTGS1, SMN, or PHAX. In contrast, C/D box snoRNP components concentrate into nuclear foci that partially colocalize with coilin after inhibition of U snRNP maturation. We demonstrate by siRNA-mediated depletion that coilin is required for the condensation of U snRNPs, but not C/D box snoRNP components, into nucleoplasmic foci, and also for merging these factors into canonical CBs. Altogether, our data suggest that CBs have a modular structure with distinct domains for spliceosomal U snRNPs and snoRNPs.

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Assembly of the Nuclear Transcription and Processing Machinery: Cajal Bodies (Coiled Bodies) and Transcriptosomes

Molecular Biology of the Cell ◽

10.1091/mbc.10.12.4385 ◽

1999 ◽

Vol 10 (12) ◽

pp. 4385-4402 ◽

Cited By ~ 174

Author(s):

Joseph G. Gall ◽

Michel Bellini ◽

Zheng’an Wu ◽

Christine Murphy

Keyword(s):

Germinal Vesicle ◽

Cajal Bodies ◽

Oocyte Nucleus ◽

Electron Microscopic ◽

Pol Ii ◽

Processing Machinery ◽

Small Nuclear Ribonucleoprotein ◽

Coiled Bodies ◽

Pol I ◽

Pol Iii

We have examined the distribution of RNA transcription and processing factors in the amphibian oocyte nucleus or germinal vesicle. RNA polymerase I (pol I), pol II, and pol III occur in the Cajal bodies (coiled bodies) along with various components required for transcription and processing of the three classes of nuclear transcripts: mRNA, rRNA, and pol III transcripts. Among these components are transcription factor IIF (TFIIF), TFIIS, splicing factors, the U7 small nuclear ribonucleoprotein particle, the stem–loop binding protein, SR proteins, cleavage and polyadenylation factors, small nucleolar RNAs, nucleolar proteins that are probably involved in pre-rRNA processing, and TFIIIA. Earlier studies and data presented here show that several of these components are first targeted to Cajal bodies when injected into the oocyte and only subsequently appear in the chromosomes or nucleoli, where transcription itself occurs. We suggest that pol I, pol II, and pol III transcription and processing components are preassembled in Cajal bodies before transport to the chromosomes and nucleoli. Most components of the pol II transcription and processing pathway that occur in Cajal bodies are also found in the many hundreds of B-snurposomes in the germinal vesicle. Electron microscopic images show that B-snurposomes consist primarily, if not exclusively, of 20- to 30-nm particles, which closely resemble the interchromatin granules described from sections of somatic nuclei. We suggest the name pol II transcriptosome for these particles to emphasize their content of factors involved in synthesis and processing of mRNA transcripts. We present a model in which pol I, pol II, and pol III transcriptosomes are assembled in the Cajal bodies before export to the nucleolus (pol I), to the B-snurposomes and eventually to the chromosomes (pol II), and directly to the chromosomes (pol III). The key feature of this model is the preassembly of the transcription and processing machinery into unitary particles. An analogy can be made between ribosomes and transcriptosomes, ribosomes being unitary particles involved in translation and transcriptosomes being unitary particles for transcription and processing of RNA.

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