Control of early development by nuclear RNA selection

In addition to alternative nRNA splicing, the nuclear RNA to mRNA stage can also be regulated by RNA “censorship”—selecting which nuclear transcripts are processed into cytoplasmic messages. Different cells select different nuclear transcripts to be processed and sent to the cytoplasm as messenger RNA. Thus, the same pool of nuclear transcripts can give rise to different populations of cytoplasmic mRNAs in different cell types (Figure 1).

Figure 1 Regulation of ectoderm-specific gene expression by RNA processing. (A) RNA selection, whereby different nuclear RNAs are proceesed into mRNAs in some cells , but not in others. This gives the two different cells different populations of mRNAs. (B, C) CyIIIa mRNA is seen by autoradiography to be present only in the ectoderm. (B) Phase contrast micrograph. (C) In situ hybridization using a probe that binds to a CyIIIa exon. (D) The CyIIIa nuclear transcript, however, is found in both ectoderm and endoderm/mesoderm. The left lane of the gel represents RNA isolated from the gastrula ectodermal tissue; the right lane represents RNA isolated from endodermal and mesodermal tissues. The upper band is the RNA bound by a probe that binds to an intron sequence (which should be found only in the nucleus) of CyIIIa. The lower band represents the RNA bound by a probe complementary to an exon sequence. The presence of the intron indicates that the CyIIIa nuclear RNA is being made in both groups of cells, even if the mRNA is seen only in the ectoderm. (From Gagnon et al. 1992, courtesy of R. and L. Angerer.)

(Click image to enlarge.)

In the late 1970s, numerous investigators found that mRNA was not the primary transcript from the genes. Rather, the initial transcript is a nuclear RNA (nRNA). This nRNA is usually many times longer than the corresponding mRNA because nRNA contains introns that get spliced out during the passage from nucleus to cytoplasm. Originally, investigators thought that whatever RNA was transcribed in the nucleus was processed into cytoplasmic mRNA. But studies of sea urchins showed that different cell types could be transcribing the same type of nuclear RNA, but processing different subsets of this population into mRNA in different types of cells (Kleene and Humphreys 1977, 1985). Wold and her colleagues (1978) showed that sequences present in sea urchin blastula messenger RNA, but absent in gastrula and adult tissue mRNA, were nonetheless present in the nuclear RNA of the gastrula and adult tissues.

More genes are transcribed in the nucleus than are allowed to become mRNAs in the cytoplasm. This “censoring” of RNA transcripts has been confirmed by probing for the introns and exons of specific genes. Gagnon and his colleagues (1992) performed such an analysis on the transcripts from the SpecII and CyIIIa genes of the sea urchin Strongylocentrotus purpuratus. These genes encode calcium-binding and actin proteins respectively, which are expressed only in a particular part of the ectoderm of the sea urchin larva. Using probes that bound to an exon (which is included in the mRNA) and to an intron (which is not included in the mRNA), they found that these genes were being transcribed not only in the ectodermal cells, but also in the mesoderm and endoderm. The analysis of the CyIIIa gene showed that the concentration of introns was the same in both the gastrula ectoderm and the mesoderm/endoderm samples, suggesting that this gene was being transcribed at the same rate in the nuclei of all cell types, but was made into cytoplasmic mRNA only in ectodermal cells (see Figure 1). The unprocessed nRNA for CyIIIa is degraded while still in the nuclei of the endodermal and mesodermal cells.

Literature Cited

Gagnon, M. L., Angerer, L. M., and Angerer, R. C. 1992. Posttranscriptional regulation of ectoderm-specific gene expression in early sea urchin embryos. Development 114: 457–467.

Kleene, K. C., and Humphreys, T. 1977. Similarity of hnRNA sequences in blastula and pluteus stage sea urchin embryos. Cell 12: 143–155.

Kleene, K. C. and Humphreys, T. 1985. Transcription of similar sets of rare maternal RNAs and rare nuclear RNAs in sea urchin blastulae and adult coelomocytes. J. Embryol. Exp. Morphol. 85: 131–149.

Wold, B. J., Klein, W. H., Hough-Evans, B. R., Britten ,R. J., and Davidson., E. H. 1978. Sea urchin embryo mRNA sequences expressed in nuclear RNA of adult tissues. Cell 14: 941–950.

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