Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Splicing of long non-coding RNAs primarily depends on polypyrimidine tract and 5' splice-site sequences due to weak interactions with SR proteins

Z. Krchnáková, PK. Thakur, M. Krausová, N. Bieberstein, N. Haberman, M. Müller-McNicoll, D. Stanek,

. 2019 ; 47 (2) : 911-928. [pub] 20190125

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc19034899

Many nascent long non-coding RNAs (lncRNAs) undergo the same maturation steps as pre-mRNAs of protein-coding genes (PCGs), but they are often poorly spliced. To identify the underlying mechanisms for this phenomenon, we searched for putative splicing inhibitory sequences using the ncRNA-a2 as a model. Genome-wide analyses of intergenic lncRNAs (lincRNAs) revealed that lincRNA splicing efficiency positively correlates with 5'ss strength while no such correlation was identified for PCGs. In addition, efficiently spliced lincRNAs have higher thymidine content in the polypyrimidine tract (PPT) compared to efficiently spliced PCGs. Using model lincRNAs, we provide experimental evidence that strengthening the 5'ss and increasing the T content in PPT significantly enhances lincRNA splicing. We further showed that lincRNA exons contain less putative binding sites for SR proteins. To map binding of SR proteins to lincRNAs, we performed iCLIP with SRSF2, SRSF5 and SRSF6 and analyzed eCLIP data for SRSF1, SRSF7 and SRSF9. All examined SR proteins bind lincRNA exons to a much lower extent than expression-matched PCGs. We propose that lincRNAs lack the cooperative interaction network that enhances splicing, which renders their splicing outcome more dependent on the optimality of splice sites.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19034899
003      
CZ-PrNML
005      
20191008112956.0
007      
ta
008      
191007s2019 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1093/nar/gky1147 $2 doi
035    __
$a (PubMed)30445574
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Krchnáková, Zuzana $u Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic.
245    10
$a Splicing of long non-coding RNAs primarily depends on polypyrimidine tract and 5' splice-site sequences due to weak interactions with SR proteins / $c Z. Krchnáková, PK. Thakur, M. Krausová, N. Bieberstein, N. Haberman, M. Müller-McNicoll, D. Stanek,
520    9_
$a Many nascent long non-coding RNAs (lncRNAs) undergo the same maturation steps as pre-mRNAs of protein-coding genes (PCGs), but they are often poorly spliced. To identify the underlying mechanisms for this phenomenon, we searched for putative splicing inhibitory sequences using the ncRNA-a2 as a model. Genome-wide analyses of intergenic lncRNAs (lincRNAs) revealed that lincRNA splicing efficiency positively correlates with 5'ss strength while no such correlation was identified for PCGs. In addition, efficiently spliced lincRNAs have higher thymidine content in the polypyrimidine tract (PPT) compared to efficiently spliced PCGs. Using model lincRNAs, we provide experimental evidence that strengthening the 5'ss and increasing the T content in PPT significantly enhances lincRNA splicing. We further showed that lincRNA exons contain less putative binding sites for SR proteins. To map binding of SR proteins to lincRNAs, we performed iCLIP with SRSF2, SRSF5 and SRSF6 and analyzed eCLIP data for SRSF1, SRSF7 and SRSF9. All examined SR proteins bind lincRNA exons to a much lower extent than expression-matched PCGs. We propose that lincRNAs lack the cooperative interaction network that enhances splicing, which renders their splicing outcome more dependent on the optimality of splice sites.
650    _2
$a HeLa buňky $7 D006367
650    _2
$a lidé $7 D006801
650    12
$a introny $7 D007438
650    _2
$a pyrimidiny $x analýza $7 D011743
650    12
$a místa sestřihu RNA $7 D022821
650    12
$a sestřih RNA $7 D012326
650    _2
$a RNA dlouhá nekódující $x metabolismus $7 D062085
650    _2
$a serin-arginin sestřihové faktory $x metabolismus $7 D000068103
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Thakur, Prasoon Kumar $u Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic.
700    1_
$a Krausová, Michaela $u Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic.
700    1_
$a Bieberstein, Nicole $u Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic.
700    1_
$a Haberman, Nejc $u Computational Regulatory Genomics, MRC London Institute of Medical Sciences, London W12 0NN, UK.
700    1_
$a Müller-McNicoll, Michaela $u Institute for Cell Biology and Neuroscience, Goethe University, Frankfurt am Main, Germany.
700    1_
$a Stanek, David $u Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic.
773    0_
$w MED00003554 $t Nucleic acids research $x 1362-4962 $g Roč. 47, č. 2 (2019), s. 911-928
856    41
$u https://pubmed.ncbi.nlm.nih.gov/30445574 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20191007 $b ABA008
991    __
$a 20191008113412 $b ABA008
999    __
$a ok $b bmc $g 1451559 $s 1073449
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2019 $b 47 $c 2 $d 911-928 $e 20190125 $i 1362-4962 $m Nucleic acids research $n Nucleic Acids Res $x MED00003554
LZP    __
$a Pubmed-20191007

Najít záznam

Citační ukazatele

Možnosti archivace