sau 20 Flashcards
Show how DNA methylation patterns can be faithfully inherited when a cell divides.
Show how Histone modifications may be inherited by daughter chromosomes.
Explain why mRNAs contain sequences that control their translation
An mRNA’s lifespan is dictated by specific nucleotide sequences within the untranslated regions that lie both upstream and downstream of the protein-coding sequence. These sequences often contain binding sites for proeins that are involved in RNA degradation. But they also carry information specifying whether - and how often - the mRNA is to be translated into protein.
The binding sequence located a few nucleotide pairs upstream of the AUG codon where translation begins. This binding sequence forms base pairs with the rRNA in the small ribosomal subunit, correctly positioning the initiating AUG codon within the ribosome. Because this interaction is needed for efficient translation initiation, it provides an ideal target for translational control. By blocking - or exposeing - the ribosomebinding sequence, the cell can either inhibit - or promote the translation of an mRNA.
Specialized repressor proteins can inhibit translation by binding to specific nucleotide sequences in the 5’ utranslated region of the mRNA, thereby preventing the ribosome from finding the first AUG. When conditions change, the cell can inactivate the repressor to initiate translation of the mRNA.
Explain why regulatory RNAs control the expression of thousands of genes
Noncoding RNAs have a variety of functions. Some, such as transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs) play key structural and catalytic roles in the cell, particularly in protein synthesis. The RNA component of telomerase is crucial for the complete duplication of eukaryotic chromosomes.
Many of these noncoding RNAs have crucial roles in regulating gene expression and are therefore referred to as regulatory RNAs. These regulatory RNAs include microRNAs, small interfering RNAs, and long noncoding RNAs.
Show how A bacterial gene’s expression can be controlled by regulating translation of its mRNA.
Explain why microRNAs direct the destruction of target mRNAs
miRNAs are tiny RNA molecules that control gene expression by base-pairing with specific mRNAs and reducing both their stability and their translation into protein. miRNAs undergo processing to produce the mature, functional miRNA molecule. The mature miRNA, about 22 nucleotides in length, is packaged with specialized proteins to form and an RNA-induced silencing complex (RISC), which patrols the cytosol in search of mRNAs that are complementary in sequence to its bound miRNA. Onve a target mRNA base-airs with an miRNA, it is either destroyed immediately by a nuclease that is part of the RISC - or its translation is blocked. In the latter case, the bound mRNA molecule is delivered to a region of the cytosol where other nucleases eventually degrade it. Destruction of the mRNA releases the miRNA-bearing RISC, allowing it to seek out additional mRNA targets. Thus, a single miRNA - as part of a RISC - can eliminate one mRNA molecule after another, thereby efficiently blocking production of the encoded protein.
Explain why small interfering RNAs protect cells from infections
Some of the same components that process and pacage miRNAs also play another crucial part in the life of a cell: they serve as a powerful defense mechanism. A system is used to eliminate “foreign” RNA molecules - in particular, long, double-stranded RNA molecules. Such RNAs are rarely produced by normal genes, but they often serves as intermediates in the life cycles of viruses and in the movement of some transposable genetic elements. This form of RNA targeting, called RNA interferance (RNAi), keeps these protenially destructive elements in check.
In the first step of RNAi, double-stranded, foreign RNAs are cut into short fragments (ca. 22 nucelotide pairs in length) in the cytosol by a protein called Dicer - the same protein used to generate the double-stranded RNA intermediate in miRNA production. The resulting double-stranded RNA fragments, called small interfering RNAs (siRNAs), are then taken up by the same RISC proteins that carry miRNAs. The RISC discards one strand of the siRNA duplex and uses the remaining single-stranded RNA to seek and destroy complementary RNA molecules. In this way, the infected cell effectively turns the foreign RNA against itself.
RNAi can also selectively shut off the synthesis of foreign RNAs by the host’s RNA polymerase. In this case, the siRNAs produced by DIcer are packaged into a protein complex called RITS (forn RNA-induced transcriptional silencing). Using its single-stranded siRNA as a guide, the RITS complex attaches itself to complementary RNA seqeunces as they emerge from an actively transcriing RNA polymerase. Positioned along a genes in this way, the RITS complex then attracts proteins that covalently modify nearby histones in a way that promotes the localized formation of heterochromatin. This heterochromatin then blocks further transcription initiation at that site. Such RNAi-directed heterochromatin formation helps limit the spread of transposable genetic elements throughout the host genome.
Show how RNAi can also trigger transcriptional silencing.
Show how Long noncoding RNAs can serve as scaffolds, bringing together
proteins that function in the same cell process.
Explain why thousands of long noncoding RNAs may also regulate mammalian gene activity
The long noncoding RNAs, a class of RNA molecules that are defined as being more than 200 nucleotides in length.
One of the best understood of the long noncoding RNAs is Xist. This RNA molecules, some 17000 nucleotides long, is a key player in X-inactivation - the process by which one of the two X chromosomes in the cells of female mammals is permantly silenced. Early in development, Xist is produced by only one of the X chromosomes in each female nucleus. The transcript then “sticks around”, coating the chromosome and attracting the enzymes and chromatin-remodeling complexes that promote the formation of highly condensed heterochromatin.
Some long noncoding RNAs fold into specific, three-dimensional structures via complementary base pairing. Thse structures can serve as scaffolds, which bring together proteins that function together in a particular cell process. For example, one of the roles of the RNA molecule in telomerase - the enzyme that duplicates the ends of eukaryotic chromosomes - is to hold its different protein subunits together. By bringing togehter protein subunits, long noncoding RNAs can play important roles in many cell activities.
The discovery of this large class of RNAs reinforces the idea that a eukaryotic genome contains information that provides not only an inventory of the molecules and structures every cell must make, but also a set of instructions for how and when to assemble these parts to guide the growth and development of a complete organism.
