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A large family of Dscam genes with tandemly arrayed 5' cassettes in Chelicerata.

Yue Y, Meng Y, Ma H, Hou S, Cao G, Hong W, Shi Y, Guo P, Liu B, Shi F, Yang Y, Jin Y - Nat Commun (2016)

Bottom Line: Furthermore, extraordinary isoform diversity has been generated through a combination of alternating promoter and alternative splicing.These sDscams have a high sequence similarity with Drosophila Dscam1, and share striking organizational resemblance to the 5' variable regions of vertebrate clustered Pcdhs.Hence, our findings have important implications for understanding the functional similarities between Drosophila Dscam1 and vertebrate Pcdhs, and may provide further mechanistic insights into the regulation of isoform diversity.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry, Innovation Center for Signaling Network, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang ZJ310058, China.

ABSTRACT
Drosophila Dscam1 (Down Syndrome Cell Adhesion Molecules) and vertebrate clustered protocadherins (Pcdhs) are two classic examples of the extraordinary isoform diversity from a single genomic locus. Dscam1 encodes 38,016 distinct isoforms via mutually exclusive splicing in D. melanogaster, while the vertebrate clustered Pcdhs utilize alternative promoters to generate isoform diversity. Here we reveal a shortened Dscam gene family with tandemly arrayed 5' cassettes in Chelicerata. These cassette repeats generally comprise two or four exons, corresponding to variable Immunoglobulin 7 (Ig7) or Ig7-8 domains of Drosophila Dscam1. Furthermore, extraordinary isoform diversity has been generated through a combination of alternating promoter and alternative splicing. These sDscams have a high sequence similarity with Drosophila Dscam1, and share striking organizational resemblance to the 5' variable regions of vertebrate clustered Pcdhs. Hence, our findings have important implications for understanding the functional similarities between Drosophila Dscam1 and vertebrate Pcdhs, and may provide further mechanistic insights into the regulation of isoform diversity.

No MeSH data available.


Related in: MedlinePlus

Model of sDscamβ isoform expression.Symbols used are the same as in Fig. 1. Each variable cassette was preceded by a promoter. The expression of the specific combination of sDscam isoforms was achieved by alternative promoter activation, followed by alternative splicing. When sDscamβ was transcribed by a given promoter preceding a variable cassette (V1), both V1 and the downstream variable cassettes (V2, V3) could be spliced into the constant exon 5.
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f8: Model of sDscamβ isoform expression.Symbols used are the same as in Fig. 1. Each variable cassette was preceded by a promoter. The expression of the specific combination of sDscam isoforms was achieved by alternative promoter activation, followed by alternative splicing. When sDscamβ was transcribed by a given promoter preceding a variable cassette (V1), both V1 and the downstream variable cassettes (V2, V3) could be spliced into the constant exon 5.

Mentions: Our results indicated that not only the cap-proximal but also the downstream variable cassettes spliced to the constant exon. Based on this evidence, we propose a mechanistic framework for the selection of tandemly arrayed 5′ variable exons (Fig. 8). This extends and revises a previously proposed model for the mechanism governing the selection of tandemly arrayed 5′ variable regions41920. Interestingly, intron sequences downstream of the variable region exons of Pcdhs were frequently contained in complementary DNA (cDNA) in independently derived cDNA libraries, which were previously assumed to be truncated mRNA isoforms or correspond to trans-splicing precursors4. Considering the similarity of the 5′ gene structure of Chelicerata sDscams and vertebrate Pcdhs, we speculate that these unusual intron-containing cDNAs might be a consequence of the variable exons downstream of the cap-proximal exons spliced to the constant exon in vertebrate Pcdh genes. Therefore, our mechanistic framework might be broadly applicable to tandemly arrayed 5′ variable exons in invertebrates and vertebrates.


A large family of Dscam genes with tandemly arrayed 5' cassettes in Chelicerata.

Yue Y, Meng Y, Ma H, Hou S, Cao G, Hong W, Shi Y, Guo P, Liu B, Shi F, Yang Y, Jin Y - Nat Commun (2016)

Model of sDscamβ isoform expression.Symbols used are the same as in Fig. 1. Each variable cassette was preceded by a promoter. The expression of the specific combination of sDscam isoforms was achieved by alternative promoter activation, followed by alternative splicing. When sDscamβ was transcribed by a given promoter preceding a variable cassette (V1), both V1 and the downstream variable cassettes (V2, V3) could be spliced into the constant exon 5.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835542&req=5

f8: Model of sDscamβ isoform expression.Symbols used are the same as in Fig. 1. Each variable cassette was preceded by a promoter. The expression of the specific combination of sDscam isoforms was achieved by alternative promoter activation, followed by alternative splicing. When sDscamβ was transcribed by a given promoter preceding a variable cassette (V1), both V1 and the downstream variable cassettes (V2, V3) could be spliced into the constant exon 5.
Mentions: Our results indicated that not only the cap-proximal but also the downstream variable cassettes spliced to the constant exon. Based on this evidence, we propose a mechanistic framework for the selection of tandemly arrayed 5′ variable exons (Fig. 8). This extends and revises a previously proposed model for the mechanism governing the selection of tandemly arrayed 5′ variable regions41920. Interestingly, intron sequences downstream of the variable region exons of Pcdhs were frequently contained in complementary DNA (cDNA) in independently derived cDNA libraries, which were previously assumed to be truncated mRNA isoforms or correspond to trans-splicing precursors4. Considering the similarity of the 5′ gene structure of Chelicerata sDscams and vertebrate Pcdhs, we speculate that these unusual intron-containing cDNAs might be a consequence of the variable exons downstream of the cap-proximal exons spliced to the constant exon in vertebrate Pcdh genes. Therefore, our mechanistic framework might be broadly applicable to tandemly arrayed 5′ variable exons in invertebrates and vertebrates.

Bottom Line: Furthermore, extraordinary isoform diversity has been generated through a combination of alternating promoter and alternative splicing.These sDscams have a high sequence similarity with Drosophila Dscam1, and share striking organizational resemblance to the 5' variable regions of vertebrate clustered Pcdhs.Hence, our findings have important implications for understanding the functional similarities between Drosophila Dscam1 and vertebrate Pcdhs, and may provide further mechanistic insights into the regulation of isoform diversity.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry, Innovation Center for Signaling Network, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang ZJ310058, China.

ABSTRACT
Drosophila Dscam1 (Down Syndrome Cell Adhesion Molecules) and vertebrate clustered protocadherins (Pcdhs) are two classic examples of the extraordinary isoform diversity from a single genomic locus. Dscam1 encodes 38,016 distinct isoforms via mutually exclusive splicing in D. melanogaster, while the vertebrate clustered Pcdhs utilize alternative promoters to generate isoform diversity. Here we reveal a shortened Dscam gene family with tandemly arrayed 5' cassettes in Chelicerata. These cassette repeats generally comprise two or four exons, corresponding to variable Immunoglobulin 7 (Ig7) or Ig7-8 domains of Drosophila Dscam1. Furthermore, extraordinary isoform diversity has been generated through a combination of alternating promoter and alternative splicing. These sDscams have a high sequence similarity with Drosophila Dscam1, and share striking organizational resemblance to the 5' variable regions of vertebrate clustered Pcdhs. Hence, our findings have important implications for understanding the functional similarities between Drosophila Dscam1 and vertebrate Pcdhs, and may provide further mechanistic insights into the regulation of isoform diversity.

No MeSH data available.


Related in: MedlinePlus