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BMC Mol Biol
2010 Jun 17;11:46. doi: 10.1186/1471-2199-11-46.
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Alternative trans-splicing of Caenorhabditis elegans sma-9/schnurri generates a short transcript that provides tissue-specific function in BMP signaling.
Yin J
,
Yu L
,
Savage-Dunn C
.
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Transcription cofactors related to Drosophila Schnurri facilitate the transcriptional programs regulated by BMP signaling in C. elegans, Drosophila, Xenopus, and mouse. In different systems, Schnurri homologs have been shown to act as either agonists or antagonists of Smad function, and as either positive or negative regulators of transcription. How Schnurri proteins achieve this diversity of activities is not clear. The C. elegans sma-9/schnurri locus undergoes alternative splicing, including an unusual trans-splicing event that could generate two non-overlapping shorter transcripts. We demonstrate here that the shorter transcripts are expressed in vivo. Furthermore, we find that one of the short transcripts plays a tissue-specific role in sma-9 function, contributing to the patterning of male-specific sensory rays, but not to the regulation of body size. Based on previous results, we suggest that this transcript encodes a C-terminal SMA-9 isoform that may provide transcriptional activation activity, while full length isoforms may mediate transcriptional repression and/or activation in a context-dependent manner. The alternative trans-splicing of sma-9 may contribute to the diversity of functions necessary to mediate tissue-specific outputs of BMP signaling.
Figure 1. Structure of sma-9 transcript variants. The predicted sma-9 intron-exon structure is shown above. Arrows mark positions of nonsense codons in three sma-9 alleles. pCS386 is the most complete cDNA variant isolated to date. The two short variants represented by cDNA clones yk1285a11 (A11) and yk1237d01 (D01) are shown below. ARD: acidic residue-rich domain; NLS: nuclear localization signal.
Figure 2. Expression of sma-9 transcript variants. A. Detection of A11 and D01 transcripts using variant-specific RT-PCR over a gradient of annealing temperatures (left to right: 50°C - 55°C). The expected size of the PCR product is 330 bp for A11 and 300 bp for D01. B. Developmental profile of sma-9 transcript expression levels, as determined by qRT-PCR. Data are shown as transcript abundance relative to act-1 actin gene control, and error bars show standard deviation. See Table 1 for quantitation of transcript abundance relative to exon-9-containing control.
Figure 3. Expression levels of sma-9 transcripts in mutant backgrounds. Expression levels of sma-9 transcripts as determined by qRT-PCR. Animals were collected at the L3 stage. Data are shown as transcript abundance relative to act-1 actin gene control, and error bars show standard deviation. See Table 1 for quantitation of transcript abundance relative to exon-9-containing transcripts. (-): transcript harbors a premature termination codon. (+): transcript sequence is normal.
Figure 4. Phenotypic rescue by overexpression of sma-9 short transcripts. A. Male tail phenotypes are given as frequency of fusion of rays 8 and 9 per male tail side scored. p values were calculated using a Student's t-test. *: significant difference from no cDNA control (p < 0.05). **: highly significant difference from no cDNA control (p < 0.01). The p values for experiments with A11 cDNA overexpression showed no significant difference from controls (p = 0.59 for qc3; p = 0.16 for cc604). All strains contain him-5(e1490) to increase the proportion of males. B. Body size phenotypes. Mean body length at 96 hours after embryo collection (adult stage) is shown. Error bars show standard deviation. Note that these strains are transgenics expressing the rol-6 marker that influences body length, so all comparisons are made between heat-shocked animals and no heat shock control rather than using a nontransgenic control. p values were calculated using a Student's t-test. **: highly significant difference from no heat shock control (p < 0.01).
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