Faculty Opinions recommendation of Re-splicing of mature mRNA in cancer cells promotes activation of distant weak alternative splice sites.

2012 ◽  
Author(s):  
Juan Valcárcel ◽  
Sophie Bonnal
Keyword(s):  
Cancer Cells ◽  
Alternative Splice ◽  
Splice Sites ◽  
Mature Mrna

scholarly journals Re-splicing of mature mRNA in cancer cells promotes activation of distant weak alternative splice sites

2012 ◽  
Vol 40 (16) ◽  
pp. 7896-7906 ◽  
Author(s):  
Toshiki Kameyama ◽  
Hitoshi Suzuki ◽  
Akila Mayeda
Keyword(s):  
Cancer Cells ◽  
Alternative Splice ◽  
Splice Sites ◽  
Mature Mrna

scholarly journals The Exon Junction Complex Core Represses Cancer-Specific Mature mRNA Re-Splicing: A Potential Key Role in Terminating Splicing

2021 ◽  
Vol 22 (12) ◽  
pp. 6519
Author(s):  
Yuta Otani ◽  
Ken-ichi Fujita ◽  
Toshiki Kameyama ◽  
Akila Mayeda
Keyword(s):  
Cancer Cells ◽  
Control Factor ◽  
Exon Junction Complex ◽  
Core Component ◽  
Normal Cells ◽  
Knock Down ◽  
Exon Junction ◽  
Mature Mrna ◽  
Complex Core ◽  
Specific Mrna

Using TSG101 pre-mRNA, we previously discovered cancer-specific re-splicing of mature mRNA that generates aberrant transcripts/proteins. The fact that mRNA is aberrantly re-spliced in various cancer cells implies there must be an important mechanism to prevent deleterious re-splicing on the spliced mRNA in normal cells. We thus postulated that mRNA re-splicing is controlled by specific repressors, and we searched for repressor candidates by siRNA-based screening for mRNA re-splicing activity. We found that knock-down of EIF4A3, which is a core component of the exon junction complex (EJC), significantly promoted mRNA re-splicing. Remarkably, we could recapitulate cancer-specific mRNA re-splicing in normal cells by knock-down of any of the core EJC proteins, EIF4A3, MAGOH, or RBM8A (Y14), implicating the EJC core as the repressor of mRNA re-splicing often observed in cancer cells. We propose that the EJC core is a critical mRNA quality control factor to prevent over-splicing of mature mRNA.

scholarly journals Amount of RNA secondary structure required to induce an alternative splice.

1987 ◽  
Vol 7 (9) ◽  
pp. 3194-3198 ◽  
Author(s):  
D Solnick ◽  
S I Lee
Keyword(s):  
Alternative Splicing ◽  
Secondary Structure ◽  
Alternative Splice ◽  
Rna Secondary Structure ◽  
Secondary Structures ◽  
Splice Sites ◽  
Perfect Complementarity ◽  
Set Up

We set up an alternative splicing system in vitro in which the relative amounts of two spliced RNAs, one containing and the other lacking a particular exon, were directly proportional to the length of an inverted repeat inserted into the flanking introns. We then used the system to measure the effect of intramolecular complementarity on alternative splicing in vivo. We found that an alternative splice was induced in vivo only when the introns contained more than approximately 50 nucleotides of perfect complementarity, that is, only when the secondary structure was much more stable than most if not all possible secondary structures in natural mRNA precursors. We showed further that intron insertions containing long complements to splice sites and a branch point inhibited splicing in vitro but not in vivo. These results raise the possibility that in cells most pre-mRNA secondary structures either are not maintained long enough to influence splicing choices, or never form at all.

scholarly journals Assessment of branch point prediction tools to predict physiological branch points and their alteration by variants

2019 ◽  
Author(s):  
Raphael Leman ◽  
Hélène Tubeuf ◽  
Sabine Raad ◽  
Isabelle Tournier ◽  
Céline Derambure ◽  
...  
Keyword(s):  
Branch Point ◽  
Mrna Splicing ◽  
Large Set ◽  
Branch Points ◽  
Splice Sites ◽  
Prediction Tools ◽  
Mature Mrna ◽  
Bioinformatics Tools ◽  
The Impact

Abstract Background: Branch points (BPs) map within short motifs upstream of acceptor splice sites (3’ss) and are essential for splicing of pre-mature mRNA. Several BP-dedicated bioinformatics tools, including HSF, SVM-BPfinder, BPP, Branchpointer, LaBranchoR and RNABPS were developed during the last decade. Here, we evaluated their capability to detect the position of BPs, and also to predict the impact on splicing of variants occurring upstream of 3’ss. Results: We used a large set of constitutive and alternative human 3’ss collected from Ensembl (n = 264,787 3’ss) and from in-house RNAseq experiments (n = 51,986 3’ss). We also gathered an unprecedented collection of functional splicing data for 120 variants (62 unpublished) occurring in BP areas of disease-causing genes. Branchpointer showed the best performance to detect the relevant BPs upstream of constitutive and alternative 3’ss (99.48 % and 65.84 % accuracies, respectively). For variants occurring in a BP area, BPP emerged as having the best performance to predict effects on mRNA splicing, with an accuracy of 89.17 %. Conclusions: Our investigations revealed that Branchpointer was optimal to detect BPs upstream of 3’ss, and that BPP was most relevant to predict splicing alteration due to variants in the BP area. Keywords: Branch Point, Prediction, RNA, Benchmark, HSF, SVM-BPfinder, BPP, Branchpointer, LaBranchoR, RNABPS, Variants

A novel computational method for the identification of plant alternative splice sites

2013 ◽  
Vol 431 (2) ◽  
pp. 221-224 ◽  
Author(s):  
Ying Cui ◽  
Jiuqiang Han ◽  
Dexing Zhong ◽  
Ruiling Liu
Keyword(s):  
Alternative Splice ◽  
Computational Method ◽  
Splice Sites

CHARACTERIZATION OF THE SPLICE SITES IN GT–AG AND GC–AG INTRONS IN HIGHER EUKARYOTES USING FULL-LENGTH cDNAs

2004 ◽  
Vol 02 (02) ◽  
pp. 309-331 ◽  
Author(s):  
SUMIE KITAMURA–ABE ◽  
HITOMI ITOH ◽  
TAKANORI WASHIO ◽  
AKIHIRO TSUTSUMI ◽  
MASARU TOMITA
Keyword(s):  
Alternative Splice ◽  
Splice Site ◽  
Consensus Sequence ◽  
Full Length ◽  
Splice Sites ◽  
Consensus Sequences ◽  
Full Length Cdna ◽  
Strong Consensus ◽  
Higher Eukaryotes

For the purpose of analyzing the relation between the splice sites and the order of introns, we conducted the following analysis for the GT–AG and GC–AG splice site groups. First, the pre-mRNAs of H. sapiens, M. musculus, D. melanogaster, A. thaliana and O. sativa were sampled by mapping the full-length cDNA to the genomes. Next, the consensus sequences at different regions of pre-mRNAs were analyzed in the five species. We also investigated the mononucleotide and dinucleotide frequencies in the extensive regions around the 5' splice sites (5'ss) and 3' splice sites (3'ss). As a result, differential frequencies of nucleotides at the first 5'ss in both the GT–AG and GC–AG splice site groups were observed in A. thaliana and O. sativa pre-mRNAs. The trend, which indicates that GC 5'ss possess strong consensus sequences, was observed not only in mammalian pre-mRNAs but also in the pre-mRNAs of D. melanogaster, A. thaliana and O. sativa. Furthermore, we examined the consensus sequences of the constitutive and alternative splice sites. It was suggested that in the case of the alternative GC–AG introns, the tendency to have a weak consensus sequence at 5'ss is different between H. sapiens and M. musculus pre-mRNAs.

scholarly journals Imprecise excision of the Caenorhabditis elegans transposon Tc1 creates functional 5' splice sites.

1994 ◽  
Vol 14 (5) ◽  
pp. 3426-3433 ◽  
Author(s):  
B Carr ◽  
P Anderson
Keyword(s):  
Caenorhabditis Elegans ◽  
Splice Site ◽  
General Characteristic ◽  
Chain Gene ◽  
Splice Sites ◽  
Wild Type ◽  
Reading Frame ◽  
Intron Splice ◽  
Mature Mrna ◽  
Imprecise Excision

Imprecise excision of the Caenorhabditis elegans transposon Tc1 from a specific site of insertion within the unc-54 myosin heavy chain gene generates either wild-type or partial phenotypic revertants. Wild-type revertants and one class of partial revertants contain insertions of four nucleotides in the unc-54 third exon (Tc1 "footprints"). Such revertants express large amounts of functional unc-54 myosin despite having what would appear to be frameshifting insertions in the unc-54 third exon. We demonstrate that these Tc1 footprints act as efficient 5' splice sites for removal of the unc-54 third intron. Splicing of these new 5' splice sites to the normal third intron splice acceptor removes the Tc1 footprint from the mature mRNA and restores the normal translational reading frame. Partial revertant unc-54(r661), which contains a single nucleotide substitution relative to the wild-type gene, is spliced similarly, except that the use of its new 5' splice site creates a frameshift in the mature mRNA rather than removing one. In all of these revertants, two alternative 5' splice sites are available to remove intron 3. We determined the relative efficiency with which each alternative 5' splice site is used by stabilizing frameshifted mRNAs with smg(-) genetic backgrounds. In all cases, the upstream member of the two alternative sites is used preferentially (> 75% utilization). This may reflect an inherent preference of the splicing machinery for the upstream member of two closely spaced 5' splice sites. Creation of new 5' splice sites may be a general characteristic of Tc1 insertion and excision events.

scholarly journals The STAR/GSG Family Protein rSLM-2 Regulates the Selection of Alternative Splice Sites

2000 ◽  
Vol 276 (12) ◽  
pp. 8665-8673 ◽  
Author(s):  
Oliver Stoss ◽  
Manuela Olbrich ◽  
Annette M. Hartmann ◽  
Harald König ◽  
John Memmott ◽  
...  
Keyword(s):  
Alternative Splice ◽  
Splice Sites ◽  
Family Protein ◽  
Selection Of

scholarly journals Splicing removes the Caenorhabditis elegans transposon Tc1 from most mutant pre-mRNAs.

1996 ◽  
Vol 16 (1) ◽  
pp. 422-429 ◽  
Author(s):  
A M Rushforth ◽  
P Anderson
Keyword(s):  
Caenorhabditis Elegans ◽  
Negative Selection ◽  
Target Gene ◽  
Mrna Processing ◽  
Chain Gene ◽  
Splice Sites ◽  
Heavy Chain Gene ◽  
Myosin Heavy Chain Gene ◽  
Mature Mrna

The transposable element Tc1 is responsible for most spontaneous mutations that occur in many Caenorhabditis elegans strains. We analyzed the abundance and sequence of mRNAs expressed from five different Tc1 insertions within either hlh-1 (a MyoD homolog) or unc-54 (a myosin heavy chain gene). Each of the mutants expresses substantial quantities of mature mRNA in which most or all of Tc1 has been removed by splicing. Such mRNAs contain small insertions of Tc1 sequences and/or deletions of target gene sequences at the resulting spliced junctions. Most of these mutant mRNAs do not contain premature stop codons, and many are translated in frame to produce proteins that are functional in vivo. The number and variety of splice sites used to remove Tc1 from these mutant pre-mRNAs are remarkable. Two-thirds of the Tc1-containing introns removed from hlh-1 and unc-54 lack either the 5'-GU or AG-3' dinucleotides typically found at the termini of eukaryotic introns. We conclude that splicing to remove Tc1 from mutant pre-mRNAs allows many Tc1 insertions to be phenotypically silent. Such mRNA processing may help Tc1 escape negative selection.

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