Coupling of transcription and RNA decay Flashcards

1
Q

What are we traditionally taught about gene expression in eukaryotes?

A

Transcription and RNA decay are independent events.

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2
Q

How many factors impact the fate of an mRNA?

A

7

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3
Q

How does polyA tail length impact the fate of an mRNA?

A

(In eukaryotes) transcripts with longer polyA tails are less susceptible to degradation because the 3’ end is protected.

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4
Q

How does splicing rate impact the fate of an mRNA?

A

Slow splicing = more frequent degradation. E.g. ribosomal proteins are spliced quickly and not degraded.

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5
Q

How does rate of nuclear export impact the fate of an mRNA?

A

Slow export = more frequent degradation.

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6
Q

How does RNA sequence impact the fate of an mRNA?

A

Specific sequences recruit RBPs e.g. which help recruit decay machinery to RNA. Often in the 3’ UTR.

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7
Q

How does RNA structure impact the fate of an mRNA?

A

Highly structured mRNAs tend to have longer half-lives e.g. stable stem loop at the beginning or end blocks nucleases.

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8
Q

How does codon sequence impact the fate of an mRNA?

A

mRNAs with many rare codons are not efficiently translated due to low frequency of these tRNAs; get degraded faster as ribosome pausing triggers decay.

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9
Q

How do ncRNAs impact the fate of an mRNA?

A

ncRNAs. miRNAs, bacterial sRNAs. Act in cis or in trans. Bind 3’ UTR and dictate translation efficiency and decay factor recruitment.

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10
Q

What are we traditionally taught about RNA decay in eularyotes?

A

Specific factors (RBPs) bind to sequences in the 3’ UTR, and they recruit or block nucleases ie promote or block decay.

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11
Q

What are new theories about RNA decay pointing to?

A

The fate of the mRNA can be dictated by cis-acting elements that are NOT part of the mRNA sequence (only the DNA).

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12
Q

What are theories coupling transcription to degradation?

A
  • Polymerase subunits assist in mRNA degradation in the cytoplasm.
  • The promoter sequence can determine the half-life of an mRNA.
  • Transcription factors recruit RNA-binding proteins to mRNAs that regulate the decay of the mRNA in the cytoplasm.
  • Transcription factor itself binds to mRNAs that regulate the decay of the mRNA in the cytoplasm.
  • Promoter elements can determine the sub-cellular localisation of the mRNA and how well it is translated.
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13
Q

What are the mechanisms of nuclear and cytoplasmic RNA decay in eukaryotes?

A
  • Nuclear RNA decay
  • Cytoplasmic RNA decay (cytoplasmic decay factors and P bodies and stress bodies).
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14
Q

How does mRNA circularise?

A

The eIF cap binding complex interacts with the Pab1 proteins bound to the polyA tail.

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15
Q

Why does mRNA circularise?

A

To make translation circular; makes it easier for ribosomes to reinitiate translation by bringing them into close proximity with the promoter when they dissociate. Also allows cell to distinguish between faulty and correct mRNAs.

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16
Q

How is circular mRNA targeted for degradation?

A

The polyA tail is digested by specific exosomal enzyme complexes (Pan2/3 and Ccr4/Not), which displaces Pab1.

17
Q

How is circular mRNA degraded?

A

Trimming of the polyA tail and Pab1 displacement This provides access to different RNA decay factors (e.g. the exosome) which can then degrade the full mRNA.