Alternative splicing impacts microRNA regulation within coding regions
Аутори
Hackl, Lena MariaFenn, Amit
Louadi1, Zakaria
Baumbach, Jan
Kacprowski, Tim
List, Markus
Tsoy, Olg
Остала ауторства
Morić, IvanaĐorđević, Valentina
Конференцијски прилог (Објављена верзија)
,
© 2023 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
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MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate post-transcriptional
gene expression by binding to specific target sites. Approximately 95% of human multi-exon
genes can be spliced alternatively, which enables the production of functionally diverse
transcripts and proteins from a single gene. In complex diseases, such as cancer, gene but also
miRNA dysregulation plays a significant role. According to most studies miRNAs preferably
bind to 3’-untranslated regions of mRNA. However, through alternative splicing, transcripts
might lose exons harboring miRNA target sites and, hence, become unresponsive to miRNA
regulation.
To check this hypothesis, we studied the role of miRNA target sites in both coding and noncoding
regions using six cancer data sets from The Cancer Genome Atlas (TCGA). First, we predicted
miRNA target sites on mRNAs from their sequence using TarPmiR. For our analysis, we focused
on miRNAs whose expression was negatively correlated with gene... expression (as evidence
for active regulation) as well as genes that were at least moderately expressed and showed
evidence of alternative splicing. We chose different subsets of transcripts to differentiate the
effects of target sites in different gene regions. To check whether alternative splicing interferes
with miRNA regulation, we trained linear regression models to predict miRNA expression from
transcript expression. Using nested models, we compared the predictive power of transcripts
with miRNA target sites to that of transcripts without target sites in the investigated gene
region. For all six cancer data sets and all subsets, models containing transcripts with target
sites predicted miRNA abundance significantly better.
We conclude that alternative splicing does interfere with miRNA regulation by skipping exons
with miRNA target sites within the coding region.
Кључне речи:
alternative splicing / miRNA / machine learning / nested models / cancerИзвор:
4th Belgrade Bioinformatics Conference, 2023, 4, 61-61Издавач:
- Belgrade : Institute of molecular genetics and genetic engineering
Напомена:
- Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 2023
Колекције
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Hackl, Lena Maria AU - Fenn, Amit AU - Louadi1, Zakaria AU - Baumbach, Jan AU - Kacprowski, Tim AU - List, Markus AU - Tsoy, Olg PY - 2023 UR - https://belbi.bg.ac.rs/ UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2001 AB - MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate post-transcriptional gene expression by binding to specific target sites. Approximately 95% of human multi-exon genes can be spliced alternatively, which enables the production of functionally diverse transcripts and proteins from a single gene. In complex diseases, such as cancer, gene but also miRNA dysregulation plays a significant role. According to most studies miRNAs preferably bind to 3’-untranslated regions of mRNA. However, through alternative splicing, transcripts might lose exons harboring miRNA target sites and, hence, become unresponsive to miRNA regulation. To check this hypothesis, we studied the role of miRNA target sites in both coding and noncoding regions using six cancer data sets from The Cancer Genome Atlas (TCGA). First, we predicted miRNA target sites on mRNAs from their sequence using TarPmiR. For our analysis, we focused on miRNAs whose expression was negatively correlated with gene expression (as evidence for active regulation) as well as genes that were at least moderately expressed and showed evidence of alternative splicing. We chose different subsets of transcripts to differentiate the effects of target sites in different gene regions. To check whether alternative splicing interferes with miRNA regulation, we trained linear regression models to predict miRNA expression from transcript expression. Using nested models, we compared the predictive power of transcripts with miRNA target sites to that of transcripts without target sites in the investigated gene region. For all six cancer data sets and all subsets, models containing transcripts with target sites predicted miRNA abundance significantly better. We conclude that alternative splicing does interfere with miRNA regulation by skipping exons with miRNA target sites within the coding region. PB - Belgrade : Institute of molecular genetics and genetic engineering C3 - 4th Belgrade Bioinformatics Conference T1 - Alternative splicing impacts microRNA regulation within coding regions EP - 61 SP - 61 VL - 4 UR - https://hdl.handle.net/21.15107/rcub_imagine_2001 ER -
@conference{ author = "Hackl, Lena Maria and Fenn, Amit and Louadi1, Zakaria and Baumbach, Jan and Kacprowski, Tim and List, Markus and Tsoy, Olg", year = "2023", abstract = "MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate post-transcriptional gene expression by binding to specific target sites. Approximately 95% of human multi-exon genes can be spliced alternatively, which enables the production of functionally diverse transcripts and proteins from a single gene. In complex diseases, such as cancer, gene but also miRNA dysregulation plays a significant role. According to most studies miRNAs preferably bind to 3’-untranslated regions of mRNA. However, through alternative splicing, transcripts might lose exons harboring miRNA target sites and, hence, become unresponsive to miRNA regulation. To check this hypothesis, we studied the role of miRNA target sites in both coding and noncoding regions using six cancer data sets from The Cancer Genome Atlas (TCGA). First, we predicted miRNA target sites on mRNAs from their sequence using TarPmiR. For our analysis, we focused on miRNAs whose expression was negatively correlated with gene expression (as evidence for active regulation) as well as genes that were at least moderately expressed and showed evidence of alternative splicing. We chose different subsets of transcripts to differentiate the effects of target sites in different gene regions. To check whether alternative splicing interferes with miRNA regulation, we trained linear regression models to predict miRNA expression from transcript expression. Using nested models, we compared the predictive power of transcripts with miRNA target sites to that of transcripts without target sites in the investigated gene region. For all six cancer data sets and all subsets, models containing transcripts with target sites predicted miRNA abundance significantly better. We conclude that alternative splicing does interfere with miRNA regulation by skipping exons with miRNA target sites within the coding region.", publisher = "Belgrade : Institute of molecular genetics and genetic engineering", journal = "4th Belgrade Bioinformatics Conference", title = "Alternative splicing impacts microRNA regulation within coding regions", pages = "61-61", volume = "4", url = "https://hdl.handle.net/21.15107/rcub_imagine_2001" }
Hackl, L. M., Fenn, A., Louadi1, Z., Baumbach, J., Kacprowski, T., List, M.,& Tsoy, O.. (2023). Alternative splicing impacts microRNA regulation within coding regions. in 4th Belgrade Bioinformatics Conference Belgrade : Institute of molecular genetics and genetic engineering., 4, 61-61. https://hdl.handle.net/21.15107/rcub_imagine_2001
Hackl LM, Fenn A, Louadi1 Z, Baumbach J, Kacprowski T, List M, Tsoy O. Alternative splicing impacts microRNA regulation within coding regions. in 4th Belgrade Bioinformatics Conference. 2023;4:61-61. https://hdl.handle.net/21.15107/rcub_imagine_2001 .
Hackl, Lena Maria, Fenn, Amit, Louadi1, Zakaria, Baumbach, Jan, Kacprowski, Tim, List, Markus, Tsoy, Olg, "Alternative splicing impacts microRNA regulation within coding regions" in 4th Belgrade Bioinformatics Conference, 4 (2023):61-61, https://hdl.handle.net/21.15107/rcub_imagine_2001 .