Page 65 - Academic Press Encyclopedia of Physical Science and Technology 3rd Molecular Biology

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Encyclopedia of Physical Science and Technology EN006H-655 June 29, 2001 21:21

514 Gene Expression, Regulation of

FIGURE 11 The cascade of regulated alternative splicing events controlling Sxl, transformer, and double-sex ex-
pression in Drosophila melanogaster. The positions of translational stop codons that will cause premature termination
of protein synthesis are indicated by Stop. See text for further details.

by biochemical assays have been shown to specify the this may be analogous to Rho-dependent transcription ter-

position of the 3 end of a mRNA (Fig. 12). Thus, an mination in bacteria.
almost invariable AAUAAA sequence located 25–30 nu-
cleotides upstream of the cleavage site and a GU-rich se-
2. Regulation of Gene Expression at the Level
quence located within 50 nucleotides downstream of the
of Alternative Poly(A) Site Usage

cleavage–polyadenylation site are critical for 3 end for-
mation. The AAUAAA sequence, which resembles the In addition to control of alternative RNA splicing, eukary-
AT-rich TATA box important for transcription initiation, otic cells frequently use alternative poly(A) site usage to
binds the essential cleavage–polyadenylation specificity further increase the coding capacity of a gene. As de-
factor (CPSF). The GU-rich sequence binds the cleavage– scribed above, the 3 end of a eukaryotic mRNA is gener-

stimulatory factor (CStF). In addition, two cleavage fac- ated by an endonucleolytic cleavage of the primary tran-
tors, CFI and CFII, and the poly(A) polymerase (PAP) script rather than termination of transcription. This means
assemble to form an active enzyme complex that cleaves that the RNA polymerase transcribing a gene may pass
the growing RNA chain and catalyzes the addition of the by several potential poly(A) sites before terminating tran-
200- to 250-nucleotide poly(A) tail. The transcribing RNA scription. Thus, the selection of different poly(A) signals
polymerase terminates RNA synthesis in an ill-defined se- in a precursor-RNA can be used to regulate gene expres-
quence downstream of the cleavage–polyadenylation site. sion. For example, if the first poly(A) signal is ignored,
However, the cleavage–polyadenylation reaction has been a second poly(A) signal further downstream in a tran-
shown to be required for transcription termination, sug- scription unit may be used to incorporate novel exons into
gesting that breakage of the primary transcript is coupled the mRNA. As an example of this type of regulation, the
to termination of transcription, possibly through the ac- production of secreted or membrane-bound immunoglob-

tion of 5 exonucleases that degrade the downstream RNA ulin M (IgM) is described. When a hematopoietic stem cell
chain generated by the cleavage reaction. Mechanistically, differentiates to a pre-B lymphocyte it produces IgM as an