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Cajal body-specific small nuclear RNAs: a novel class of 2'-O-methylation and pseudouridylation guide RNAs.

ABSTRACT: Cajal (coiled) bodies are conserved subnuclear organelles that are present in the nucleoplasm of both animal and plant cells. Although Cajal bodies were first described nearly 100 years ago, their function has remained largely speculative. Here, we describe a novel class of human small nuclear RNAs that localize specifically to Cajal bodies. The small Cajal body-specific RNAs (scaRNAs) are predicted or have already been demonstrated to function as guide RNAs in site-specific synthesis of 2'-O-ribose-methylated nucleotides and pseudouridines in the RNA polymerase II-transcribed U1, U2, U4 and U5 spliceosomal small nuclear RNAs (snRNAs). Our results provide strong support for the idea that the Cajal body, this mysterious nuclear organelle, provides the cellular locale for post-transcriptional modification of spliceosomal snRNAs.

SUBMITTER: Darzacq X

PROVIDER: S-EPMC126017 | biostudies-literature | 2002 Jun

REPOSITORIES: biostudies-literature

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Cajal body-specific small nuclear RNAs: a novel class of 2'-O-methylation and pseudouridylation guide RNAs.

Darzacq Xavier X Jády Beáta E BE Verheggen Céline C Kiss Arnold M AM Bertrand Edouard E Kiss Tamás T

The EMBO journal 20020601 11

Cajal (coiled) bodies are conserved subnuclear organelles that are present in the nucleoplasm of both animal and plant cells. Although Cajal bodies were first described nearly 100 years ago, their function has remained largely speculative. Here, we describe a novel class of human small nuclear RNAs that localize specifically to Cajal bodies. The small Cajal body-specific RNAs (scaRNAs) are predicted or have already been demonstrated to function as guide RNAs in site-specific synthesis of 2'-O-ri ...[more]

PMID: 12032087

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Project description:Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs involved in the maturation of other RNA molecules and generally located in the introns of host genes. It is now emerging that altered sno/scaRNAs expression may play a pathological role in cancer. This study elucidates the patterns of sno/scaRNAs expression in multiple myeloma (MM), by profiling puri?ed malignant plasma cells from 55 MMs, 8 secondary plasma cell leukemias (sPCL) and 4 normal controls. Overall, a global sno/scaRNAs down-regulation was found in MMs and at more extent in sPCLs compared to normal plasma cells. Whereas SCARNA22 resulted the only sno/scaRNA characterizing the TC4 MM, TC2 group displayed a distinct sno/scaRNA signature overexpressing members of SNORD115 and SNORD116 families located in a region finely regulated by imprinting mechanism at 15q11. However, the imprinting center resulted overall hypomethylated in MMs independently of the SNORD115 and SNORD116 expression levels. Finally, integrative analyses with available gene expression and genome-wide data revealed the occurrence of significant sno/scaRNAs/host genes co-expression and the putative influence of allelic imbalances on specific snoRNAs expression. Our data extend the current view of sno/scaRNAs deregulation in cancer and add novel information into the bio-molecular complexity of plasma cell dyscrasias. This series of microarray experiments contains the gene expression profiles of purified plasma cells (PCs) obtained from 55 multiple myeloma (MM) and 8 secondary plasma cell leukemia (sPCL) at diagnosis. PCs were purified from bone marrow samples using CD138 immunomagnetic microbeads according to the manufacturer's instructions (MidiMACS system, Miltenyi Biotec); the purity of the positively selected PCs was assessed by morphology and flow cytometry and was > 90% in all cases. 5.5 micrograms of single-stranded DNA target obtained from 100 ng of purified total RNA was fragmented and then labeled using the WT Terminal Labeling Kit according to the standard Affymetrix protocol (GeneChipÂ® Whole Transcript (WT) Sense Target Labeling Assay Manual). The fragmented labeled single-stranded DNA target was hybridized for 16 hours and 30 minutes at 45Â°C on GeneChipÂ® Gene 1.0 ST array according to the standard Affymetrix protocol. Washing and scanning were performed using GeneChip System of Affymetrix (GeneChip Hybridization Oven 640, GeneChip Fluidics Station 450 and GeneChip Scanner 7G). The raw intensity expression values were processed by Robust Multi-array Average (RMA) complete procedure with the re-mapped Chip Definition Files (CDF) from BrainArray libraries version 15.0.0 available at http://brainarray.mbni.med.umich.edu/Brainarray/Database/CustomCDF/15.0.0/entrezg.asp.

Dataset Information

Cajal body-specific small nuclear RNAs: a novel class of 2'-O-methylation and pseudouridylation guide RNAs.

Publications

Cajal body-specific small nuclear RNAs: a novel class of 2'-O-methylation and pseudouridylation guide RNAs.

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