RNA processing sau 25 Flashcards

1
Q

Describe how mRNAs are processed in the nucleus

A

Because bacteria lack a nucleus, their DNA is directly exposed to the cytosol, which contains the ribosomes on which protein synthesis takes place. As an mRNA molecule in a bacterium starts to be synthesized, ribosomes immediately attach to the free 5ʹ end of the RNA transcript and begin translating it into protein.

In eukaryotic cells, by contrast, DNA is enclosed within the nucleus, which
is where transcription takes place. Translation, however, occurs on ribosomes
that are located in the cytosol. So, before a eukaryotic mRNA
can be translated into protein, it must be transported out of the nucleus
through small pores in the nuclear envelope. And before it can be exported to the cytosol, a eukaryotic RNA must go through several RNA processing steps, which include capping, splicing, and polyadenylation. The enzymes responsible for RNA processing ride on the phosphorylated tail of eukaryotic RNA polymerase II as it synthesizes an RNA molecule, and they process the transcript as it
emerges from the polymerase

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2
Q

Describe hpw phosphorylation of the tail of RNA polymerase II
allows RNA-processing proteins to assemble there.

A
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3
Q

Describe the two processing steps

A

Two of these processing steps, capping and polyadenylation, occur on all
RNA transcripts destined to become mRNA molecules.

  1. RNA capping modifies the 5ʹ end of the RNA transcript, the part of
    the RNA that is synthesized first. The RNA cap includes an atypical
    nucleotide: a guanine (G) nucleotide bearing a methyl group is
    attached to the 5ʹ end of the RNA in an unusual way. In eukaryotic cells, capping takes
    place after RNA polymerase II has produced about 25 nucleotides of
    RNA, long before it has completed transcribing the whole gene.
  2. Polyadenylation provides a newly transcribed mRNA with a
    special structure at its 3ʹ end. The 3′ end of a eukaryotic mRNA is first trimmed
    by an enzyme that cuts the RNA chain at a particular sequence of
    nucleotides. The transcript is then finished off by a second enzyme
    that adds a series of repeated adenine (A) nucleotides to the trimmed
    end. This poly-A tail is generally a few hundred nucleotides long.

These two modifications—capping and polyadenylation—increase the
stability of a eukaryotic mRNA molecule, facilitate its export from the
nucleus to the cytosol, and generally mark the RNA molecule as an
mRNA. They are also used by the protein-synthesis machinery to make
sure that both ends of the mRNA are present and that the message is
therefore complete before protein synthesis begins.

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4
Q

Describe how Eukaryotic mRNA
molecules are modified by capping and
polyadenylation.

A
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5
Q

Describe how Eukaryotic and bacterial
genes are organized differently.

A
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6
Q

Descirbe how in eukaryotes, protein-codring genes are interrupted by noncoding sequences called introns

A

Most protein-coding eukaryotic genes, in contrast, have their coding sequences interrupted by long, noncoding, intervening sequences called introns. The scattered pieces of coding sequence—called expressed sequences or exons—are usually
shorter than the introns, and they often represent only a small fraction of
the total length of the gene. Some protein-coding eukaryotic genes lack introns altogether, some have only a few, but most have many. Note that the terms “exon” and “intron” apply to both the DNA and the corresponding RNA sequences.

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7
Q

Describe how introns are removed from Pre-mRNAs by RNA splicing

A

To produce an mRNA in a eukaryotic cell, the entire length of the gene,
introns as well as exons, is transcribed into RNA. After capping, and as
RNA polymerase II continues to transcribe the gene, RNA splicing begins.
In this process, the introns are removed from the newly synthesized RNA
and the exons are stitched together. Each transcript ultimately receives a
poly-A tail; in many cases, this happens after splicing, whereas in other
cases, it occurs before the final splicing reactions have been completed.
Once a transcript has been spliced and its 5ʹ and 3ʹ ends have been modified,
the RNA is now a functional mRNA molecule that can leave the
nucleus and be translated into protein. Before these steps are completed,
the RNA transcript is known as a precursor-mRNA or pre-mRNA for short.
How does the cell determine which parts of the RNA transcript to remove
during splicing? Unlike the coding sequence of an exon, most of the
nucleotide sequence of an intron is unimportant. Although there is little
overall resemblance between the nucleotide sequences of different introns, each intron contains a few short nucleotide sequences that act
as cues for its removal from the pre-mRNA. These special sequences are
found at or near each end of the intron and are the same or very similar in
all introns.

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8
Q

Describe how Most proteincoding
human genes are
broken into multiple exons
and introns.

A
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9
Q

Describe how Special nucleotide sequences in a pre-mRNA transcript signal the
beginning and the end of an intron.

A
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10
Q

Describe which molecules carry out RNA splicing

A

RNA splicing is carried out largely by RNA molecules rather than proteins. These RNA
molecules, called small nuclear RNAs (snRNAs), are packaged with
additional proteins to form small nuclear ribonucleoproteins (snRNPs, pronounced
“snurps”). The snRNPs recognize splice-site sequences through
complementary base-pairing between their RNA components and the
sequences in the pre-mRNA, and they carry out the chemistry of splicing. RNA molecules that catalyze reactions in this way are known as ribozymes. Together, these snRNPs form the core of the spliceosome, the large assembly of RNA and protein molecules that carries out RNA splicing
in the nucleus.

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11
Q

Describe how An intron in a pre-mRNA molecule forms a branched
structure during RNA splicing.

A
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12
Q

Describe how Splicing is carried out by a
collection of RNA–protein complexes
called snRNPs.

A
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13
Q

Alternative splicing

A

About 95% of human genes are thought to undergo alternative
splicing. Thus RNA splicing enables eukaryotes to increase the
already enormous coding potential of their genomes.

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14
Q

Describe how Some pre-mRNAs undergo alternative RNA splicing to produce
different mRNAs and proteins from the same gene.

A
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15
Q

With so many components required to produce and process every one of the RNA molecules that are being transcribed, how do all these factors manage to find one another?

A

The enzymes responsible for RNA processing ride on the phosphorylated tail of eukaryotic RNA polymerase II as it synthesizes an RNA molecule, so that the RNA transcript can be processed as it is being synthesized. In addition to this association,
RNA polymerases and RNA-processing proteins also form loose
molecular aggregates—generally termed intracellular condensates—that
act as “factories” for the production of RNA. These factories, which bring
together the numerous RNA polymerases, RNA-processing components,
and the genes being expressed, are large enough to be seen microscopically.

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16
Q

How, then, does the cell distinguish
between the relatively rare mature mRNA molecules it needs to
export to the cytosol and the overwhelming amount of debris generated
by RNA processing?

A

The transport of mRNA from the nucleus to the cytosol is highly selective: only correctly processed mRNAs are exported and therefore available to be translated. This selective transport is mediated by nuclear pore complexes, which connect the nucleoplasm with the cytosol and act as gates that control which macromolecules can enter or leave the nucleus. To be “export ready,” an
mRNA molecule must be bound to an appropriate set of proteins, each
of which recognizes different parts of a mature mRNA molecule. These
proteins include poly-A-binding proteins, a cap-binding complex, and
proteins that bind to mRNAs that have been appropriately spliced. The entire set of bound proteins, rather than any single protein, ultimately determines whether an mRNA molecule will leave the nucleus. The “waste RNAs” that remain behind in the nucleus are degraded there, and their nucleotide building blocks are reused for transcription.

17
Q

Describe how mRNA Molecules Are Eventually Degraded in the Cytosol

A

Because a single mRNA molecule can be translated into protein many
times, the length of time that a mature mRNA molecule
persists in the cell greatly influences the amount of protein it produces. Each mRNA molecule is eventually degraded into nucleotides by ribonucleases
(RNAses) present in the cytosol, but the lifespans of mRNA
molecules differ considerably—depending on the nucleotide sequence of
the mRNA and the type of cell. These different lifespans are in part controlled by nucleotide sequences in the mRNA itself, most often in the portion of RNA called the 3ʹ untranslated region, which lies between the 3ʹ end of the coding sequence and
the poly-A tail. will be produced. In general, proteins made in large amounts, such as β-globin, are translated from mRNAs that have long lifespans, whereas proteins made in smaller amounts, or whose levels must change rapidly in response to signals, are typically synthesized from short-lived mRNAs.

18
Q

Describe how A specialized set of RNA-binding proteins signals that a completed mRNA is ready for export to the cytosol.

A