Universität zu Köln

Ptok, Johannes, Mueller, Lisa, Ostermann, Philipp Niklas, Ritchie, Anastasia, Dilthey, Alexander T., Theiss, Stephan ORCID: 0000-0002-5881-6067 and Schaal, Heiner (2021). Modifying splice site usage with ModCon: Maintaining the genetic code while changing the underlying mRNP code. Comp. Struct. Biotechnol. J.., 19. S. 3069 - 3077. AMSTERDAM: ELSEVIER. ISSN 2001-0370

Full text not available from this repository.

Abstract

Codon degeneracy of amino acid sequences permits an additional mRNP code layer underlying the genetic code that is related to RNA processing. In pre-mRNA splicing, splice site usage is determined by both intrinsic strength and sequence context providing RNA binding sites for splicing regulatory proteins. In this study, we systematically examined modification of splicing regulatory properties in the neighborhood of a GT site, i.e. potential splice site, without altering the encoded amino acids. We quantified the splicing regulatory properties of the neighborhood around a potential splice site by its Splice Site HEXplorer Weight (SSHW) based on the HEXplorer score algorithm. To systematically modify GT site neighborhoods, either minimizing or maximizing their SSHW, we designed the novel stochastic optimization algorithm ModCon that applies a genetic algorithm with stochastic crossover, insertion and random mutation elements supplemented by a heuristic sliding window approach. To assess the achievable range in SSHW in human splice donors without altering the encoded amino acids, we applied ModCon to a set of 1000 randomly selected Ensembl annotated human splice donor sites, achieving substantial and accurate changes in SSHW. Using ModCon optimization, we successfully switched splice donor usage in a splice site competition reporter containing coding sequences from FANCA, FANCB or BRCA2, while retaining their amino acid coding information. The ModCon algorithm and its R package implementation can assist in reporter design by either introducing novel splice sites, silencing accidental, undesired splice sites, and by generally modifying the entire mRNP code while maintaining the genetic code. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ptok, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Ostermann, Philipp Niklas UNSPECIFIED UNSPECIFIED UNSPECIFIED Ritchie, Anastasia UNSPECIFIED UNSPECIFIED UNSPECIFIED Dilthey, Alexander T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Theiss, Stephan UNSPECIFIED orcid.org/0000-0002-5881-6067 UNSPECIFIED Schaal, Heiner UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-572603
DOI:	10.1016/j.csbj.2021.05.033
Journal or Publication Title:	Comp. Struct. Biotechnol. J..
Volume:	19
Page Range:	S. 3069 - 3077
Date:	2021
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	2001-0370
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language U1 SNRNA Multiple languages Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57260