Limits...
The spliced leader trans-splicing mechanism in different organisms: molecular details and possible biological roles.

Bitar M, Boroni M, Macedo AM, Machado CR, Franco GR - Front Genet (2013)

Bottom Line: We have analyzed 157 SLe sequences from 148 species from seven phyla and found a high degree of conservation among the sequences of species from the same phylum, although no considerable similarity seems to exist between sequences of species from different phyla.When analyzing case studies, we found evidence that a given SLe will always be related to a given set of transcripts in different species from the same phylum, and therefore, different SLe sequences from the same species would regulate different sets of transcripts.It represents a comprehensive study concerning various species and different characteristics of this important post-transcriptional regulatory mechanism.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Genética Bioquímica, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais Belo Horizonte, Brazil.

ABSTRACT
THE SPLICED LEADER (SL) IS A GENE THAT GENERATES A FUNCTIONAL NCRNA THAT IS COMPOSED OF TWO REGIONS: an intronic region of unknown function (SLi) and an exonic region (SLe), which is transferred to the 5' end of independent transcripts yielding mature mRNAs, in a process known as spliced leader trans-splicing (SLTS). The best described function for SLTS is to solve polycistronic transcripts into monocistronic units, specifically in Trypanosomatids. In other metazoans, it is speculated that the SLe addition could lead to increased mRNA stability, differential recruitment of the translational machinery, modification of the 5' region or a combination of these effects. Although important aspects of this mechanism have been revealed, several features remain to be elucidated. We have analyzed 157 SLe sequences from 148 species from seven phyla and found a high degree of conservation among the sequences of species from the same phylum, although no considerable similarity seems to exist between sequences of species from different phyla. When analyzing case studies, we found evidence that a given SLe will always be related to a given set of transcripts in different species from the same phylum, and therefore, different SLe sequences from the same species would regulate different sets of transcripts. In addition, we have observed distinct transcript categories to be preferential targets for the SLe addition in different phyla. This work sheds light into crucial and controversial aspects of the SLTS mechanism. It represents a comprehensive study concerning various species and different characteristics of this important post-transcriptional regulatory mechanism.

No MeSH data available.


Related in: MedlinePlus

Different splicing mechanisms. (A) Variations of cis- and trans-splicing processes. (B) The spliced leader trans-splicing mechanism. This panel depicts the overall SLTS mechanism, in which an invariant exon (the SLe) is added to an unrelated, independently produced transcript, yielding a mature mRNA. Cis-splicing is also represented for comparison. The SLe molecule contains a hypermodified cap, whereas the SLi usually harbors an Sm-protein binding site.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3795323&req=5

Figure 1: Different splicing mechanisms. (A) Variations of cis- and trans-splicing processes. (B) The spliced leader trans-splicing mechanism. This panel depicts the overall SLTS mechanism, in which an invariant exon (the SLe) is added to an unrelated, independently produced transcript, yielding a mature mRNA. Cis-splicing is also represented for comparison. The SLe molecule contains a hypermodified cap, whereas the SLi usually harbors an Sm-protein binding site.

Mentions: Splicing has been known for a long time as a post-transcriptional process for regulation of gene expression [reviewed by Gilbert (1978); Padgett et al. (1986) and further by several other authors]. To date, there are different known variants of both cis and trans-splicing mechanisms (Figure 1A). Cis-splicing differs from trans-splicing on the genomic origin of the transcripts involved. While cis-splicing is concerned with transcripts from a single gene, trans-splicing mechanisms act by connecting transcripts of otherwise unrelated genes (Figure 1). In the spliced leader trans-splicing (SLTS) mechanism, the exonic portion of the spliced leader (SLe) transcript is transferred to the 5′ end of unrelated transcripts to yield a mature mRNA (Boothroyd and Cross, 1982) and reviewed by Liang et al. (2003) (Figure 1B). As first observed in trypanosomatids, its best described function is to resolve polycistronic transcripts into monocistronic units (Sather and Agabian, 1985) and reviewed by Preußer et al. (2012). Subsequently, SLTS was demonstrated to occur in other euglenozoans (Tessier et al., 1991) and several organisms, such as rotifers (Pouchkina-Stantcheva and Tunnacliffe, 2005), cnidarians (Stover and Steele, 2001), chordata (Vandenberghe et al., 2001), nematoda (Krause and Hirsh, 1987), platyhelminthes (Rajkovic et al., 1990), and dinoflagellates (Lidie and Van Dolah, 2007). Different biological roles have been proposed for this mechanism, such as: (i) enhancing translation of trans-spliced transcripts by providing a specialized (hypermethylated) 5′ cap structure for trans-spliced transcripts, (ii) stabilizing the mRNAs, and (iii) removing regulatory elements from the outron, what has been called 5′ UTR sanitization (Hastings, 2005; Matsumoto et al., 2010). In a recent work Nilsson and collaborators (Nilsson et al., 2010) discuss possible functions for the SLTS mechanism in Trypanosoma brucei. According to the authors, the differential insertion of the SLe sequence in alternative acceptor sites of genes could lead to: (i) translation blockage when the SLe insertion is upstream the protein start codon; (ii) alteration of protein subcellular location, when signaling sequences are eliminated by SLe insertion; (iii) inclusion or exclusion of uORFs or other regulatory elements from 5′ end of transcripts; and (iv) translation of alternative ORFs. It has also been speculated that SLe addition could lead to increased mRNA stability, differential recruitment of the translational machinery, modification of the 5′ UTR or a combination of those effects [reviewed by Hastings (2005); Stover et al. (2006); Lasda and Blumenthal (2011)]. From a recent study concerning the SLTS mechanism in the flatworm Schistosoma mansoni Mourão et al., (2013), our group identified transcripts under trans-splicing regulation in different life-cycle stages, suggesting that the SLTS could account for differential protein levels and protein repertories in different stages and/or environmental conditions. Although important aspects of the SLTS mechanism in this parasite were elucidated, several other questions regarding this mechanism in S. mansoni and other organisms remained unanswered. These questions surround the existence of conserved motifs within SL sequences from different species, the possible emergence of SLTS in more complex taxa as plants and mammals, the role of the SLTS mechanism in different organisms, the peculiarities of the set of transcripts under the control of a given SLe and the structural aspects of the SL molecule.


The spliced leader trans-splicing mechanism in different organisms: molecular details and possible biological roles.

Bitar M, Boroni M, Macedo AM, Machado CR, Franco GR - Front Genet (2013)

Different splicing mechanisms. (A) Variations of cis- and trans-splicing processes. (B) The spliced leader trans-splicing mechanism. This panel depicts the overall SLTS mechanism, in which an invariant exon (the SLe) is added to an unrelated, independently produced transcript, yielding a mature mRNA. Cis-splicing is also represented for comparison. The SLe molecule contains a hypermodified cap, whereas the SLi usually harbors an Sm-protein binding site.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3795323&req=5

Figure 1: Different splicing mechanisms. (A) Variations of cis- and trans-splicing processes. (B) The spliced leader trans-splicing mechanism. This panel depicts the overall SLTS mechanism, in which an invariant exon (the SLe) is added to an unrelated, independently produced transcript, yielding a mature mRNA. Cis-splicing is also represented for comparison. The SLe molecule contains a hypermodified cap, whereas the SLi usually harbors an Sm-protein binding site.
Mentions: Splicing has been known for a long time as a post-transcriptional process for regulation of gene expression [reviewed by Gilbert (1978); Padgett et al. (1986) and further by several other authors]. To date, there are different known variants of both cis and trans-splicing mechanisms (Figure 1A). Cis-splicing differs from trans-splicing on the genomic origin of the transcripts involved. While cis-splicing is concerned with transcripts from a single gene, trans-splicing mechanisms act by connecting transcripts of otherwise unrelated genes (Figure 1). In the spliced leader trans-splicing (SLTS) mechanism, the exonic portion of the spliced leader (SLe) transcript is transferred to the 5′ end of unrelated transcripts to yield a mature mRNA (Boothroyd and Cross, 1982) and reviewed by Liang et al. (2003) (Figure 1B). As first observed in trypanosomatids, its best described function is to resolve polycistronic transcripts into monocistronic units (Sather and Agabian, 1985) and reviewed by Preußer et al. (2012). Subsequently, SLTS was demonstrated to occur in other euglenozoans (Tessier et al., 1991) and several organisms, such as rotifers (Pouchkina-Stantcheva and Tunnacliffe, 2005), cnidarians (Stover and Steele, 2001), chordata (Vandenberghe et al., 2001), nematoda (Krause and Hirsh, 1987), platyhelminthes (Rajkovic et al., 1990), and dinoflagellates (Lidie and Van Dolah, 2007). Different biological roles have been proposed for this mechanism, such as: (i) enhancing translation of trans-spliced transcripts by providing a specialized (hypermethylated) 5′ cap structure for trans-spliced transcripts, (ii) stabilizing the mRNAs, and (iii) removing regulatory elements from the outron, what has been called 5′ UTR sanitization (Hastings, 2005; Matsumoto et al., 2010). In a recent work Nilsson and collaborators (Nilsson et al., 2010) discuss possible functions for the SLTS mechanism in Trypanosoma brucei. According to the authors, the differential insertion of the SLe sequence in alternative acceptor sites of genes could lead to: (i) translation blockage when the SLe insertion is upstream the protein start codon; (ii) alteration of protein subcellular location, when signaling sequences are eliminated by SLe insertion; (iii) inclusion or exclusion of uORFs or other regulatory elements from 5′ end of transcripts; and (iv) translation of alternative ORFs. It has also been speculated that SLe addition could lead to increased mRNA stability, differential recruitment of the translational machinery, modification of the 5′ UTR or a combination of those effects [reviewed by Hastings (2005); Stover et al. (2006); Lasda and Blumenthal (2011)]. From a recent study concerning the SLTS mechanism in the flatworm Schistosoma mansoni Mourão et al., (2013), our group identified transcripts under trans-splicing regulation in different life-cycle stages, suggesting that the SLTS could account for differential protein levels and protein repertories in different stages and/or environmental conditions. Although important aspects of the SLTS mechanism in this parasite were elucidated, several other questions regarding this mechanism in S. mansoni and other organisms remained unanswered. These questions surround the existence of conserved motifs within SL sequences from different species, the possible emergence of SLTS in more complex taxa as plants and mammals, the role of the SLTS mechanism in different organisms, the peculiarities of the set of transcripts under the control of a given SLe and the structural aspects of the SL molecule.

Bottom Line: We have analyzed 157 SLe sequences from 148 species from seven phyla and found a high degree of conservation among the sequences of species from the same phylum, although no considerable similarity seems to exist between sequences of species from different phyla.When analyzing case studies, we found evidence that a given SLe will always be related to a given set of transcripts in different species from the same phylum, and therefore, different SLe sequences from the same species would regulate different sets of transcripts.It represents a comprehensive study concerning various species and different characteristics of this important post-transcriptional regulatory mechanism.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Genética Bioquímica, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais Belo Horizonte, Brazil.

ABSTRACT
THE SPLICED LEADER (SL) IS A GENE THAT GENERATES A FUNCTIONAL NCRNA THAT IS COMPOSED OF TWO REGIONS: an intronic region of unknown function (SLi) and an exonic region (SLe), which is transferred to the 5' end of independent transcripts yielding mature mRNAs, in a process known as spliced leader trans-splicing (SLTS). The best described function for SLTS is to solve polycistronic transcripts into monocistronic units, specifically in Trypanosomatids. In other metazoans, it is speculated that the SLe addition could lead to increased mRNA stability, differential recruitment of the translational machinery, modification of the 5' region or a combination of these effects. Although important aspects of this mechanism have been revealed, several features remain to be elucidated. We have analyzed 157 SLe sequences from 148 species from seven phyla and found a high degree of conservation among the sequences of species from the same phylum, although no considerable similarity seems to exist between sequences of species from different phyla. When analyzing case studies, we found evidence that a given SLe will always be related to a given set of transcripts in different species from the same phylum, and therefore, different SLe sequences from the same species would regulate different sets of transcripts. In addition, we have observed distinct transcript categories to be preferential targets for the SLe addition in different phyla. This work sheds light into crucial and controversial aspects of the SLTS mechanism. It represents a comprehensive study concerning various species and different characteristics of this important post-transcriptional regulatory mechanism.

No MeSH data available.


Related in: MedlinePlus