RNA core) have remained the same. The role of SRP in the cell is to bind signal peptides that are located
at the terminus of nascent membrane and secretory proteins.^61 After forming a complex with the signal
sequence, SRP guides the entire ribosome/peptide complex to a receptor site on the endoplasmic reticu-
lum (ER), where the remainder of the protein is synthesized, while it is transported simultaneously
through (or into) the ER membrane.
SRP RNA contains an “S” domain that is highly conserved in all kingdoms (Figure 7.32). In Archaea
and Eukaryotes, this has been appended to an “Alu domain” RNA. Intriguingly, this Alu domain is the same
sequence that is encoded by the eukaryotic mobile genetic element of the same name (Section 7.5.1), and
this connection between SRP and genomic plasticity remains a subject of great interest. The SRP RNA is
bound by conserved proteins (such as the GTPases SRP54 and SR) that are involved in assembly and
function of the particle.
7.5 RNAs and Epigenetic Phenomena
Genomes and gene expression are constantly being altered by processes that are “outside” the normal
processes of DNA replication, RNA metabolism, and protein expression. These “epigenetic phenomena”
often involve specialized RNA molecules that play a major role in the evolution and metabolism of diverse
organisms.
7.5.1 RNA Mobile Elements
Genomes are not static environments. Nor do genomes necessarily evolve through small changes that
accumulate slowly over time. Rather, genomes often undergo massive changes, the most potent effectors of
which are mobile genetic elements, or transposons (Section 6.8.3). While the zoology of mobile elements
is diverse,^62 the retrotransposonsrepresent a subset of RNA molecules that are of particular interest
because of their remarkable mobility mechanisms and their profound influence on eukaryotic genomes.
These RNAs assemble with cofactor proteins to form RNPs that encode, or depend upon, reverse tran-
scriptases (RT)to produce stable DNA copies of their progeny.
7.5.1.1 Mammalian L1 and Alu Elements. A stunning 25% of human DNA, by weight, encodes
two RNA molecules (L1, 15%; and Alu, 10%) in millions of copies that have radically altered the organ-
ization of mammalian genomes. Although only a fraction of these copies are functional, the mobilization
of L1 and Alu elementscauses significant genomic rearrangement, which can lead to cancer and other
diseases.^63
The L1 gene encodes a large RNA that is 6000 nucleotides in length. This polyadenylated transcript
contains a 5-UTR and two reading frames (ORF1 and ORF2) that encode proteins essential for L1 trans-
position. The proteins ORF1p and ORF2p form an RNP by binding to substructures in the L1 RNA.
Functional L1 RNPs are then imported into the nucleus, where they attack the host genome through a
process that involves reverse transcription of L1 RNA by the ORF2p. RTs such as ORF2p are polymerases
that can synthesize DNA from an RNA template. They are important for the replication and genomic inte-
gration of many mobile elements and for retroviruses, such as HIV (Section 6.4.6).
The Alu element is a remarkably small RNA (300 nucleotides) that originated from the 7SL RNA
of SRP (Figure 7.32, Section 7.4). Perhaps due to a similarity in the RNA binding properties of SRP and
L1 proteins, 7SL RNA is believed to have recruited the L1 transposition apparatus, which allowed it to
replicate and proliferate as the Alu mobile element. Alu elements lack ORFs for proteins that stimulate
mobility, and therefore they continue to depend on L1 for mobilization and proliferation in the human
genome.
7.5.1.2 Group II Intron Retrotransposons. A second family of retrotransposon mobilizes a catalytic
intron that is commonly found in the organellar genes of plants, fungi, yeast, and also in bacteria. Group II
intronsare self-splicing RNAs (Section 7.2), which contain an ORF that encodes a multifunctional
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