Post-transcriptional modification of spliceosomal RNAs is normal in SMN-deficient cells

Deryusheva, Svetlana; Choleza, Maria; Barbarossa, Adrien; Gall, Joseph G.; Bordonne, Rémy

doi:10.1261/rna.030106.111

Cited by 39 publications

(51 citation statements)

References 39 publications

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“…3). The 5′ portion contains an impressive number of post-transcriptional modifications including 14 pseudouridylations and 10 methylated nucleotides [47]–[49]. In contrast, no modifications are identified downstream of position 90 of RNU2, and this domain contains more extensive secondary structure, particularly when the precursor sequence is included.…”

Section: Resultsmentioning

confidence: 99%

Alternative Processing of the U2 Small Nuclear RNA Produces a 19–22nt Fragment with Relevance for the Detection of Non-Small Cell Lung Cancer in Human Serum

Catherinne¹,

Delfour²,

Gouin

et al. 2013

PLoS ONE

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RNU2 exists in two functional forms (RNU2-1 and RNU2-2) distinguishable by the presence of a unique 4-bases motif. Detailed investigation of datasets obtained from deep sequencing of five human lung primary tumors revealed that both forms express at a high rate a 19–22nt fragment (miR-U2-1 and -2) from its 3′ region and contains the 4-bases motif. Deep sequencing of independent pools of serum samples from healthy donors and lung cancer patients revealed that miR-U2-1 and -2 are pervasively processed in lung tissue by means of endonucleolytic cleavages and stably exported to the blood. Then, microarrays hybridization experiments of matched normal/tumor samples revealed a significant over-expression of miR-U2-1 in 14 of 18 lung primary tumors. Subsequently, qRT-PCR of miR-U2-1 using serum from 62 lung cancer patients and 96 various controls demonstrated that its expression levels identify lung cancer patients with 79% sensitivity and 80% specificity. miR-U2-1 expression correlated with the presence or absence of lung cancer in patients with chronic obstructive pulmonary disease (COPD), other diseases of the lung – not cancer, and in healthy controls. These data suggest that RNU2-1 is a new bi-functional ncRNA that produces a 19–22nt fragment which may be useful in detecting lung cancer non-invasively in high risk patients.

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Section: Resultsmentioning

confidence: 99%

Alternative Processing of the U2 Small Nuclear RNA Produces a 19–22nt Fragment with Relevance for the Detection of Non-Small Cell Lung Cancer in Human Serum

Catherinne¹,

Delfour²,

Gouin

et al. 2013

PLoS ONE

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“…In contrast, U6 snRNA, whose known guide RNAs concentrate in nucleoli (Tycowski et al 1998;Ganot et al 1999;Darzacq et al 2002), could not be modified when targeted to CBs . The postulate that snRNA modification requires targeting to CBs became untenable when it was shown that snRNA modification still takes place in mutant cells that lack CBs Nizami et al 2010b;Deryusheva et al 2012). Furthermore, snRNAs can be efficiently modified in vitro in cell-free systems (Jády and Kiss 2001;Ma et al 2005;Deryusheva and Gall 2009).…”

Section: Introductionmentioning

confidence: 99%

Novel small Cajal-body-specific RNAs identified in Drosophila: probing guide RNA function

Deryusheva

Gall

2013

RNA

Self Cite

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The spliceosomal small nuclear RNAs (snRNAs) are modified post-transcriptionally by introduction of pseudouridines and 2 ′ -Omethyl modifications, which are mediated by box H/ACA and box C/D guide RNAs, respectively. Because of their concentration in the nuclear Cajal body (CB), these guide RNAs are known as small CB-specific (sca) RNAs. In the cell, scaRNAs are associated with the WD-repeat protein WDR79. We used coimmunoprecipitation with WDR79 to recover seven new scaRNAs from Drosophila cell lysates. We demonstrated concentration of these new scaRNAs in the CB by in situ hybridization, and we verified experimentally that they can modify their putative target RNAs. Surprisingly, one of the new scaRNAs targets U6 snRNA, whose modification is generally assumed to occur in the nucleolus, not in the CB. Two other scaRNAs have dual guide functions, one for an snRNA and one for 28S rRNA. Again, the modification of 28S rRNA is assumed to take place in the nucleolus. These findings suggest that canonical scaRNAs may have functions in addition to their established role in modifying U1, U2, U4, and U5 snRNAs. We discuss the likelihood that processing by scaRNAs is not limited to the CB.

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“…This complex is implicated in the nucleocytoplasmic transport of small nuclear RNAs (snRNAs) and in their maturation to small nuclear ribonucleoproteins (snRNPs) as part of the spliceosomal complex (Akten et al, 2011;Deryusheva et al, 2012;Fischer et al, 1997;Leung et al, 2011;Liu et al, 1997;Makarov et al, 2012;Massenet et al, 2002;Matera and Shpargel, 2006;Sebbag-Sznajder et al, 2012). Studies using different models of SMA have suggested that the severity of the disease could correlate with the inefficiency of snRNP maturation, and as a consequence, to defective splicing of target pre-mRNAs (Chari et al, 2009;Gabanella et al, 2007;Imlach et al, 2012;Lotti et al, 2012;Pellizzoni, 2007;Winkler et al, 2005;Workman et al, 2009;Zhang et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

The tudor protein survival motor neuron (SMN) is a chromatin-binding protein that interacts with methylated histone H3 lysine 79

Sabra¹,

Texier²,

Maalouf³

et al. 2013

Journal of Cell Science

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SummarySpinal muscular atrophy (SMA) is a muscular disease characterized by the death of motoneurons, and is a major genetic cause of infant mortality. Mutations in the SMN1 gene, which encodes the protein survival motor neuron (SMN), are responsible for the disease. SMN belongs to the Tudor domain protein family, whose members are known to interact with methylated arginine (R) or lysine (K) residues. SMN has well-defined roles in the metabolism of small non-coding ribonucleoproteins (snRNPs) and spliceosome activity. We previously showed that SMN relocated to damaged interphase centromeres, together with the Cajal-body-associated proteins coilin and fibrillarin, during the so-called interphase centromere damage response (iCDR). Here we reveal that SMN is a chromatin-binding protein that specifically interacts with methylated histone H3K79, a gene expression-and splicing-associated histone modification. SMN relocation to damaged centromeres requires its functional Tudor domain and activity of the H3K79 methyltransferase DOT1L. In vitro pulldown assays showed that SMN interacts with H3K79me1,2 at its functional Tudor domain. Chromatin immunoprecipitation confirmed that SMN binds to H3K79me1,2-containing chromatin in iCDR-induced cells. These data reveal a novel SMN property in the detection of specific chromatin modifications, and shed new light on the involvement of a putative epigenetic dimension to the occurrence of SMA.

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Post-transcriptional modification of spliceosomal RNAs is normal in SMN-deficient cells

Cited by 39 publications

References 39 publications

Alternative Processing of the U2 Small Nuclear RNA Produces a 19–22nt Fragment with Relevance for the Detection of Non-Small Cell Lung Cancer in Human Serum

Alternative Processing of the U2 Small Nuclear RNA Produces a 19–22nt Fragment with Relevance for the Detection of Non-Small Cell Lung Cancer in Human Serum

Novel small Cajal-body-specific RNAs identified in Drosophila: probing guide RNA function

The tudor protein survival motor neuron (SMN) is a chromatin-binding protein that interacts with methylated histone H3 lysine 79

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