T.P.1.11 Correction of endogenous DMPK transcripts by chimeric U2 small nuclear RNA – artificial trans-splicing molecules as therapeutic strategy in dystrophia myotonica type 1

2009 ◽  
Vol 19 (8-9) ◽  
pp. 579-580
Author(s):  
H.Y. Chen ◽  
P. Kathirvel ◽  
Q.B. Xiong ◽  
P.S. Lai ◽  
W.C. Yee
Keyword(s):  
Therapeutic Strategy ◽  
Small Nuclear Rna ◽  
Dystrophia Myotonica ◽  
Trans Splicing ◽  
Nuclear Rna

scholarly journals Loss of U11 small nuclear RNA in the developing mouse limb results in micromelia

Development ◽  
2020 ◽  
Vol 147 (21) ◽  
pp. dev190967
Author(s):  
Kyle D. Drake ◽  
Christopher Lemoine ◽  
Gabriela S. Aquino ◽  
Anna M. Vaeth ◽  
Rahul N. Kanadia
Keyword(s):  
Cell Cycle ◽  
Limb Development ◽  
Intron Retention ◽  
Size Control ◽  
Small Nuclear Rna ◽  
Essential Components ◽  
Primordial Dwarfism ◽  
Nuclear Rna ◽  
Mouse Limb

ABSTRACTDisruption of the minor spliceosome due to mutations in RNU4ATAC is linked to primordial dwarfism in microcephalic osteodysplastic primordial dwarfism type 1, Roifman syndrome, and Lowry-Wood syndrome. Similarly, primordial dwarfism in domesticated animals is linked to positive selection in minor spliceosome components. Despite being vital for limb development and size regulation, its role remains unexplored. Here, we disrupt minor spliceosome function in the developing mouse limb by ablating one of its essential components, U11 small nuclear RNA, which resulted in micromelia. Notably, earlier loss of U11 corresponded to increased severity. We find that limb size is reduced owing to elevated minor intron retention in minor intron-containing genes that regulate cell cycle. As a result, limb progenitor cells experience delayed prometaphase-to-metaphase transition and prolonged S-phase. Moreover, we observed death of rapidly dividing, distally located progenitors. Despite cell cycle defects and cell death, the spatial expression of key limb patterning genes was maintained. Overall, we show that the minor spliceosome is required for limb development via size control potentially shared in disease and domestication.

trans-spliced Caenorhabditis elegans mRNAs retain trimethylguanosine caps

1990 ◽  
Vol 10 (4) ◽  
pp. 1764-1768
Author(s):  
R F Liou ◽  
T Blumenthal
Keyword(s):  
Caenorhabditis Elegans ◽  
Antibody Binding ◽  
Small Nuclear Rna ◽  
Nematode Caenorhabditis Elegans ◽  
Spliced Leader ◽  
C Elegans ◽  
Distinct Subset ◽  
Trans Splicing ◽  
Nuclear Rna ◽  
Spliced Leader Rna

The nematode Caenorhabditis elegans has an unusual small nuclear RNA, containing a 100-nucleotide RNA molecule, spliced leader RNA, which donates its 5' 22 nucleotides to a variety of recipient RNAs by a trans-splicing reaction. The spliced leader RNA has a 5' trimethylguanosine (TMG) cap, which becomes the 5' end of trans-spliced mRNAs. We found that mature trans-spliced mRNAs were immunoprecipitable with anti-TMG cap antibodies and that TMG-containing dinucleotides specifically competed with the trans-spliced mRNAs for antibody binding. We also found that these mRNAs retained their TMG caps throughout development and that the TMG-capped mRNAs were polysome associated. Since the large majority of C. elegans mRNAs are not trans-spliced, the addition of the spliced leader and its TMG cap to a limited group of recipient RNAs may create a functionally distinct subset of mRNAs.

scholarly journals Correction of dystrophia myotonica type 1 pre-mRNA transcripts by artificial trans-splicing

Gene Therapy ◽  
2008 ◽  
Vol 16 (2) ◽  
pp. 211-217 ◽  
Author(s):  
H Y Chen ◽  
P Kathirvel ◽  
W C Yee ◽  
P S Lai
Keyword(s):  
Dystrophia Myotonica ◽  
Trans Splicing ◽  
Mrna Transcripts

Destruction of U2, U4, or U6 small nuclear RNA blocks Trans splicing in trypanosome cells

Cell ◽  
1990 ◽  
Vol 61 (3) ◽  
pp. 459-466 ◽  
Author(s):  
Christian Tschudi ◽  
Elisabetta Ullu
Keyword(s):  
Small Nuclear Rna ◽  
Trans Splicing ◽  
Nuclear Rna

scholarly journals trans-spliced Caenorhabditis elegans mRNAs retain trimethylguanosine caps.

1990 ◽  
Vol 10 (4) ◽  
pp. 1764-1768 ◽  
Author(s):  
R F Liou ◽  
T Blumenthal
Keyword(s):  
Caenorhabditis Elegans ◽  
Antibody Binding ◽  
Small Nuclear Rna ◽  
Nematode Caenorhabditis Elegans ◽  
Spliced Leader ◽  
C Elegans ◽  
Distinct Subset ◽  
Trans Splicing ◽  
Nuclear Rna ◽  
Spliced Leader Rna

The nematode Caenorhabditis elegans has an unusual small nuclear RNA, containing a 100-nucleotide RNA molecule, spliced leader RNA, which donates its 5' 22 nucleotides to a variety of recipient RNAs by a trans-splicing reaction. The spliced leader RNA has a 5' trimethylguanosine (TMG) cap, which becomes the 5' end of trans-spliced mRNAs. We found that mature trans-spliced mRNAs were immunoprecipitable with anti-TMG cap antibodies and that TMG-containing dinucleotides specifically competed with the trans-spliced mRNAs for antibody binding. We also found that these mRNAs retained their TMG caps throughout development and that the TMG-capped mRNAs were polysome associated. Since the large majority of C. elegans mRNAs are not trans-spliced, the addition of the spliced leader and its TMG cap to a limited group of recipient RNAs may create a functionally distinct subset of mRNAs.

scholarly journals Minor spliceosome disruption causes limb growth defects without altering patterning

2020 ◽  
Author(s):  
Kyle D Drake ◽  
Christopher Lemoine ◽  
Gabriela S Aquino ◽  
Anna M Vaeth ◽  
Rahul N Kanadia
Keyword(s):  
Limb Development ◽  
Intron Retention ◽  
S Phase ◽  
Small Nuclear Rna ◽  
Potential Mechanism ◽  
Limb Patterning ◽  
Growth Defects ◽  
Primordial Dwarfism ◽  
Nuclear Rna

AbstractDisruption of the minor spliceosome causes primordial dwarfism in microcephalic osteodysplastic primordial dwarfism type 1. Similarly, primordial dwarfism in domesticated animals is linked to positive selection in minor spliceosome components. Despite the importance of minor intron splicing in limb size regulation, its role in limb development remains unexplored. Here we show that loss of U11 small nuclear RNA, an essential minor spliceosome component, results in stunted limbs that maintain patterning. Notably, earlier loss of U11 corresponded to increased severity. We find that limb size is reduced due to elevated minor intron retention in minor intron-containing genes that regulate cell cycle. Limb progenitor cells experience delayed prometaphase to metaphase transition and prolonged S-phase, resulting in death of rapidly dividing, distally located progenitors. Consequently, crucial limb patterning genes are upregulated and their expression is maintained spatially to achieve basic patterning. Overall, these findings reveal a potential mechanism shared in disease and domestication.

7SK small nuclear RNA inhibits cancer cell proliferation through apoptosis induction

Tumor Biology ◽  
2014 ◽  
Vol 36 (4) ◽  
pp. 2809-2814 ◽  
Author(s):  
Farid Keramati ◽  
Ehsan Seyedjafari ◽  
Parviz Fallah ◽  
Masoud Soleimani ◽  
Hossein Ghanbarian
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Small Nuclear Rna ◽  
Apoptosis Induction ◽  
Nuclear Rna

Isolation of a potato U6 small nuclear RNA gene

1991 ◽  
Vol 19 (3) ◽  
pp. 340S-340S
Author(s):  
YUNQIAN HU ◽  
JOHN W. S. BROWN ◽  
ROBBIE WAUGH ◽  
PHILIP C. TURNER
Keyword(s):  
Small Nuclear Rna ◽  
Nuclear Rna
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