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Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

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436 Chapter 7: Control of Gene Expression

and RNA sequences (Figure 7–79B). This behavior is similar to that of snoRNAs

(see Figure 6–41), crRNAs (see Figure 7–78), and miRNAs (see Figure 7–75), all of

which act in this way to guide protein enzymes to specific nucleic acid sequences.

In some cases, lncRNAs work simply by base-pairing, without bringing in

enzymes or other proteins. For example, a number of lncRNA genes are embedded

in protein-coding genes, but they are transcribed in the “wrong direction.”

These antisense RNAs can form complementary base pairs with the mRNA (transcribed

in the “correct” direction) and block its translation into protein (see Figure

7–66D). Other antisense lncRNAs base-pair with pre-mRNAs as they are synthesized

and change the pattern of RNA splicing by masking splice-site sequences.

Still others act as “sponges,” base-pairing with miRNAs and thereby reducing their

effects.

Finally, we note that some lncRNAs can act only in cis; that is, they affect only

the chromosome from which they are transcribed. This readily occurs when the

transcribed RNA has not yet been released from RNA polymerases (Figure 7–79C).

Many lncRNAs, however, diffuse from their site of synthesis and act in trans.

Although the best understood lncRNAs work in the nucleus, many are found in the

cytosol. The functions—if any—of the great majority of these cytosolic lncRNAs

remain undiscovered.

Summary

RNA molecules have many uses in the cell besides carrying the information needed

to specify the order of amino acids during protein synthesis. Although we have

encountered noncoding RNAs in other chapters (tRNAs, rRNAs, snoRNAs, for example),

the sheer number of noncoding RNAs produced by cells has surprised scientists.

One well understood use of noncoding RNAs occurs in RNA interference, where

guide RNAs (miRNAs, siRNAs, piRNAs) base-pair with mRNAs. RNA interference

can cause mRNAs to be either destroyed or translationally repressed. It can also

cause specific genes to be packaged into heterochromatin suppressing their transcription.

In bacteria and archaebacteria, RNA interference is used as an adaptive

immune response to destroy viruses that infect them. A large family of large noncoding

RNAs (lncRNAs) has recently been discovered. Although the function of most of

these RNAs is unknown, some serve as RNA scaffolds to bring specific proteins and

RNA molecules together to speed up needed reactions.

What we don’t know

• How is the final rate of transcription

of a gene specified by the hundreds of

proteins that assemble on its control

regions? Will we ever be able to predict

this rate from inspection of the DNA

sequences of control regions?

• How does the collection of cisregulatory

sequences embedded in a

genome orchestrate the developmental

program of a multicellular organism?

• How much of the human genome

sequence is functional, and why is the

remainder retained?

• Which of the thousands of unstudied

noncoding RNAs have functions in the

cell, and what are these functions?

• Were introns present in early cells

(and subsequently lost in some

organisms), or did they arise at later

times?

Problems

Which statements are true? Explain why or why not.

7–1 In terms of the way it interacts with DNA, the

helix–loop–helix motif is more closely related to the leucine

zipper motif than it is to the helix–turn–helix motif.

7–2 Once cells have differentiated to their final specialized

forms, they never again alter expression of their

genes.

7–3 CG islands are thought to have arisen during evolution

because they were associated with portions of the

genome that remained unmethylated in the germ line.

7–4 In most differentiated tissues, daughter cells retain

a memory of gene expression patterns that were present

in the parent cell through mechanisms that do not involve

changes in the sequence of their genomic DNA.

Discuss the following problems.

7–5 A small portion of a two-dimensional display

of proteins from human brain is shown in Figure Q7–1.

These proteins were separated on the basis of size in one

dimension and electrical charge (isoelectric point) in the

other. Not all protein spots on such displays are products

Figure Q7–1 Twodimensional

separation of

proteins from the human

brain (Problem 7–5). The

proteins were displayed

using two-dimensional

gel electrophoresis. Only

a small portion of the

protein spectrum is shown.

(Courtesy of Tim Myers and

Leigh Anderson, Large Scale

Biology Corporation.)

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smaller

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