Circular Languages Generated by Complete Splicing Systems and Pure Unitary Languages

Circular splicing systems are a formal model of a generative mechanism of circular words, inspired by a recombinant behaviour of circular DNA. Some unanswered questions are related to the computational power of such systems, and finding a characterization of the class of circular languages generated by circular splicing systems is still an open problem. In this paper we solve this problem for complete systems, which are special finite circular splicing systems. We show that a circular language L is generated by a complete system if and only if the set Lin(L) of all words corresponding to L is a pure unitary language generated by a set closed under the conjugacy relation. The class of pure unitary languages was introduced by A. Ehrenfeucht, D. Haussler, G. Rozenberg in 1983, as a subclass of the class of context-free languages, together with a characterization of regular pure unitary languages by means of a decidable property. As a direct consequence, we characterize (regular) circular languages generated by complete systems. We can also decide whether the language generated by a complete system is regular. Finally, we point out that complete systems have the same computational power as finite simple systems, an easy type of circular splicing system defined in the literature from the very beginning, when only one rule is allowed. From our results on complete systems, it follows that finite simple systems generate a class of context-free languages containing non-regular languages, showing the incorrectness of a longstanding result on simple systems

Control of human papillomavirus gene expression by alternative splicing

Human papillomaviruses possess circular double stranded DNA genomes of around 8 kb in size from which multiple mRNAs are synthesized during an infectious life cycle. Although at least three viral promoters are used to initiate transcription, viral mRNAs are largely the product of processing of pre-mRNAs by alternative splicing and polyadenylation. The HPV life cycle and viral gene expression are tightly linked to differentiation of the epithelium the virus infects: there is an orchestrated production of viral mRNAs and proteins. In this review we describe viral mRNA expression and the roles of the SR and hnRNP proteins that respectively positively and negatively regulate splicing. We discuss HPV regulation of splicing factors and detail the evidence that the papillomavirus E2 protein has splicing-related activities. We highlight the possibility that HPV-mediated control of splicing in differentiating epithelial cells may be necessary to accomplish the viral replication cycle

Splicing Systems from Past to Future: Old and New Challenges

A splicing system is a formal model of a recombinant behaviour of sets of double stranded DNA molecules when acted on by restriction enzymes and ligase. In this survey we will concentrate on a specific behaviour of a type of splicing systems, introduced by P\u{a}un and subsequently developed by many researchers in both linear and circular case of splicing definition. In particular, we will present recent results on this topic and how they stimulate new challenging investigations.Comment: Appeared in: Discrete Mathematics and Computer Science. Papers in Memoriam Alexandru Mateescu (1952-2005). The Publishing House of the Romanian Academy, 2014. arXiv admin note: text overlap with arXiv:1112.4897 by other author

On Special forms of Splicing on Arrays and Graphs

Tom Head (1987), in his pioneering work on formal language theory applied to DNA computing, introduced a new operation of splicing on strings, while proposing a model of certain recombination behaviour of DNA molecules under the action of restriction enzymes and ligases. Since then this operation has been studied in great depth giving rise to a number of theoretical results of great interest in formal language theory. Extension of this operation of splicing to higher dimensional structures such as circular words, arrays, trees and graphs have been proposed in the literature. Here we examine the effect of certain specific forms of the splicing operation applied to arrays and graphs

Genome-Wide Profiling of Circular RNAs in the Rapidly Growing Shoots of Moso Bamboo (Phyllostachys edulis).

Circular RNAs, including circular exonic RNAs (circRNA), circular intronic RNAs (ciRNA) and exon-intron circRNAs (EIciRNAs), are a new type of noncoding RNAs. Growing shoots of moso bamboo (Phyllostachys edulis) represent an excellent model of fast growth and their circular RNAs have not been studied yet. To understand the potential regulation of circular RNAs, we systematically characterized circular RNAs from eight different developmental stages of rapidly growing shoots. Here, we identified 895 circular RNAs including a subset of mutually inclusive circRNA. These circular RNAs were generated from 759 corresponding parental coding genes involved in cellulose, hemicellulose and lignin biosynthetic process. Gene co-expression analysis revealed that hub genes, such as DEFECTIVE IN RNA-DIRECTED DNA METHYLATION 1 (DRD1), MAINTENANCE OF METHYLATION (MOM), dicer-like 3 (DCL3) and ARGONAUTE 1 (AGO1), were significantly enriched giving rise to circular RNAs. The expression level of these circular RNAs presented correlation with its linear counterpart according to transcriptome sequencing. Further protoplast transformation experiments indicated that overexpressing circ-bHLH93 generating from transcription factor decreased its linear transcript. Finally, the expression profiles suggested that circular RNAs may have interplay with miRNAs to regulate their cognate linear mRNAs, which was further supported by overexpressing miRNA156 decreasing the transcript of circ-TRF-1 and linear transcripts of TRF-1. Taken together, the overall profile of circular RNAs provided new insight into an unexplored category of long noncoding RNA regulation in moso bamboo

Splicing systems and the Chomsky hierarchy

In this paper, we prove decidability properties and new results on the position of the family of languages generated by (circular) splicing systems within the Chomsky hierarchy. The two main results of the paper are the following. First, we show that it is decidable, given a circular splicing language and a regular language, whether they are equal. Second, we prove the language generated by an alphabetic splicing system is context-free. Alphabetic splicing systems are a generalization of simple and semi-simple splicin systems already considered in the literature

FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons

The RNA-binding protein FUS participates in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Here we report that FUS controls back-splicing reactions leading to circular RNA (circRNA) production. We identified circRNAs expressed in in vitro -derived mouse motor neurons (MNs) and determined that the production of a considerable number of these circRNAs is regulated by FUS. Using RNAi and overexpression of wild-type and ALS-asso- ciated FUS mutants, we directly correlate the modulation of circRNA biogenesis with alteration of FUS nuclear levels and with putative toxic gain of function activities. We also demonstrate that FUS regulates circRNA biogenesis by binding the introns flanking the back-splicing junctions and that this control can be reproduced with artificial constructs. Most circRNAs are conserved in humans and specific ones are deregulated in human-induced pluripotent stem cell-derived MNs carrying the FUS P525L mutation associated with AL

Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis

Circular RNAs (circRNAs) constitute a family of transcripts with unique structures and still largely unknown functions. Their biogenesis, which proceeds via a back-splicing reaction, is fairly well characterized, whereas their role in the modulation of physiologically relevant processes is still unclear. Here we performed expression profiling of circRNAs during in vitro differentiation of murine and human myoblasts, and we identified conserved species regulated in myogenesis and altered in Duchenne muscular dystrophy. A high-content functional genomic screen allowed the study of their functional role in muscle differentiation. One of them, circ-ZNF609, resulted in specifically controlling myoblast proliferation. Circ-ZNF609 contains an open reading frame spanning from the start codon, in common with the linear transcript, and terminating at an in-frame STOP codon, created upon circularization. Circ-ZNF609 is associated with heavy polysomes, and it is translated into a protein in a splicing-dependent and cap-independent manner, providing an example of a protein-coding circRNA in eukaryotes