Nucleic Acids in Chemistry and Biology

involves annealing of short gRNAs (which are actually encoded by specialized introns) that direct the
positioning of modifying enzymes.^48

7.2.4.3 A Critical Base Modification for Spliceosomal Function. The U2 snRNA is an integral

part of the U2 snRNP that is required for pre-mRNA splicing. A short sequence in the U2 snRNA forms
base pairs around the branch-site adenosine on pre-mRNA, thereby specifying the 2
-hydroxyl group of
this adenosine as the unique nucleophile for splicing. It is known that a highly conserved pseudouridine
pairs immediately next to the intron branch-site and that it is important for pre-mRNA splicing. NMR
studies of the U2-mRNA pairing have shown that the pseudouridine causes the branch-site adenosine to
flip out of the duplex and to present its 2
-OH group in the proper orientation for nucleophilic attack.^49
When a normal uridine is present at the same position, the branch-site adenosine stacks into the
U2-mRNA helix. Thus, a single, subtle modification on U2 snRNA changes the conformational prefer-
ences of surrounding nucleotides and may facilitate the process of pre-mRNA splicing.

7.2.5 RNA Removal and Deca y

Just as it is important to transcribe, process, and modify RNA molecules, it is important for an organism
to remove RNA molecules when they are no longer useful. Thus, there are highly regulated pathways for
the removal of damaged, improperly processed, and even over-abundant RNAs that might interfere with
desired levels of gene expression.

7.2.5.1 Ribonucleases and the Exosome. Although nucleases are found in all types of cells

and compartments, eukaryotes in particular teem with nucleases that police the structural integrity of
RNA, remove invading nucleic acids (such as viral RNAs), and help to regulate the proper quantity of

272 Chapter 7

HN NH

O

Ribose

O N

NH

S

O

Ribose

HN

N N

N

O

Ribose

HN

N N

O

Ribose

H 2 N

NH

OH

OH

N

N

Ribose

NH 2

N

H

(CH 2 ) 4 NH 3

N COO

N

DNA

O

NH 2

H 3 C

CH 3

N

N N

N

DNA

HN

lysidine

psuedouridine 4-thiouridine inosine queuosine

5-methylcytosine N^6 -methyladenine

Figure 7.24 Common modified bases in RNA and DNA. Hundreds of different base modifications have been observed.
A selection of the most common is shown here. The position of modification is highlighted with a pink
circle

http://www.ebook3000.com