Similarly, once an mRNA transcript has been completely synthesized, its 3terminus must be protected
through the process of polyadenylation^31 (Figure 7.14). Nascent transcripts contain a polyadenylation
signal sequence that is located near the 3-terminus. This sequence is bound by a set of specificity factors
and cleaved through a mechanism that remains unclear. A specialized enzyme called poly-A polymerase
then extends the 3-terminus by successive addition of adenosine residues, resulting in a poly-A tail.
Once this tail has been added, the mRNA is recognized by export factors and transported across the
nuclear membrane to the cytoplasm. Many mRNA molecules are subsequently “circularized” by proteins
that bridge the 5-cap and poly-A tail, and this plays a role in subsequent translation by the ribosome
(Figure 7.15).^32
7.2.2 Splicing and Trimming the RNA
In addition to protection of their termini, many RNA molecules undergo additional processing events. To
understand these, it is helpful to consider the schematic diagram of a eukaryotic pre-mRNA, which is
defined as a new RNA transcript that has not yet been altered in sequence. A typical pre-mRNA contains
an abundance of extra sequence that is not translated into protein (Figure 7.16, see also Figure 6.2). For
example, most eukaryotic mRNA molecules contain long sequences at each terminus. These untranslated
regions (UTRs)do not encode protein and they fold into specialized structures that help regulate transla-
tion and other functions of the message. The mRNA between the UTRs is divided into short segments of
coding RNA (exons), which contain sequences that will ultimately encode protein and which are separ-
ated by long stretches of “junk” RNA (introns) which do not encode protein, but which can have other
264 Chapter 7
Figure 7.15 The cyclization of eukaryotic mRNAs. Because factor eIF4G acts as a bridging molecule (grey), the
5 -end (bound to the eukaryotic initiation factor eIF4E, red) and the 3-end (bound to poly-A binding
protein, PAB, pink) are effectively connected in many eukaryotic messages (dark black line)
Figure 7.14 Polyadenylation. Red lines indicate continuous mRNA sequence. Pink shapes represent poly-A polymerase
and its associated proteins