Influence of mRNA Sequence on Translation

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Questions and Answers

What is the significance of Kozak sequence in translation initiation?

It helps in termination of translation

It helps in recognition of start codon

It increases the rate of translation elongation

It allows internal initiation of translation (correct)

Why do some codons have a higher chance of being translated more efficiently than others?

Due to the abundance of tRNAs for each codon (correct)

Due to the presence of a selenocysteine codon

Due to the size of the amino acid being translated

Due to the presence of a stop codon

What can sometimes be read instead of a stop codon?

A pyrrolysine codon

A methionine codon

A selenocysteine codon (correct)

A histidine codon

What is the function of the GCN4 protein?

It is a transcription factor that regulates amino acid biosynthesis genes Signup and view all the answers

What is the role of the 5'UTR in translation?

It has an influence on translation initiation Signup and view all the answers

What is the significance of the sequence context in translation?

It affects the efficiency of translation elongation Signup and view all the answers

What is the effect of eIF2 inactivation on translation?

Translation is slowed down but not completely blocked Signup and view all the answers

What is the function of the first uORF in the GCN4 mRNA?

To trap ribosomes that have started translating from the CAP Signup and view all the answers

Why is GCN4 protein not translated when there is an abundance of amino acids in the cell?

Because the ribosome is stopped by the non-permissive termination sequence Signup and view all the answers

What determines the regulation of GCN4 translation in response to amino acid availability?

The concentration of eIF2 and the distance between uORF and GCN4 Signup and view all the answers

What is the purpose of uORFs in some genes?

To regulate translation and/or mRNA stability Signup and view all the answers

What is the outcome when a ribosome reaches a non-permissive termination sequence in a uORF?

The ribosome terminates translation and dissociates from the mRNA Signup and view all the answers

What is the primary effect of uORFs on the translation of downstream reading frames?

Attenuation of translation Signup and view all the answers

What is the purpose of the Kozak sequence in the regulation of translation initiation?

To select the translation initiation site Signup and view all the answers

How can the cell regulate the translation of a protein by using alternative translation initiation sites?

By using different translation initiation sites Signup and view all the answers

What is the role of the 5’-UTR region in the regulation of translation?

To regulate the translation initiation Signup and view all the answers

What is the effect of the presence of a polyA tail on the translation of an mRNA?

It stimulates the translation of the mRNA Signup and view all the answers

How does the autogenous regulation of translation work in the case of tubulin?

Tubulin binds to its own mRNA and inhibits its translation Signup and view all the answers

What is the role of the 3’-UTR region in the regulation of translation?

To stabilize the mRNA Signup and view all the answers

What happens to the translation of an mRNA when the polyA tail is shortened?

The translation is inhibited Signup and view all the answers

What is the primary function of microtubules in mRNA trafficking?

To facilitate long-distance mRNA transport Signup and view all the answers

What is the primary role of RNA localization elements?

To target mRNAs to specific cellular locations Signup and view all the answers

What is the primary function of RNA-binding proteins in mRNA trafficking?

To facilitate mRNA transport and localization Signup and view all the answers

In which cellular region are mRNAs localized in neurons?

Dendrites and axons Signup and view all the answers

What is the primary function of kinesin in mRNA trafficking?

To move along microtubules and transport mRNA cargoes Signup and view all the answers

What is the primary role of heterogeneous nuclear ribonucleoproteins (hnRNPs) in mRNA trafficking?

To facilitate mRNA transport and localization Signup and view all the answers

Study Notes

Influence of mRNA Sequence on the 3 Stages of Translation

The formation of the initiation complex CAP depends on the Kozak sequence, and IRES sequences can allow for internal initiations.
The 5'UTR sequence influences translation, and the scanning of the initiation sequence depends on the Kozak sequence.

Elongation Stage

Ribosomes do not read all triplets with the same ease, and there is a bias in the use of codons, making some easier to read than others due to the abundance of tRNAs for each codon.
Slipping sequences can change the reading pattern, and even the presence of a bulky amino acid can hinder the exit of the peptide through the ribosomal channel.

Termination Stage

The stop triplet can sometimes be read as selenocysteine or pyrrolysine, and there are stops that allow the small subunit to remain on the mRNA and reach later reading patterns.

Regulation of Translation at the mRNA Level

5.1 Regulation with Implication of 5'UTR and ORFs

The GCN4 gene has a long 5'UTR region and two short ORFs that code for peptides without function, which trap ribosomes that have started translation from the CAP and are located before the sequence that codes for GCN4.
The first uORF terminates in a permissive termination, and the second uORF4 terminates in a non-permissive termination.

Regulation of GCN4 Translation

In conditions of sufficient amino acids, eIF2 is active, allowing the ribosome to translate and encounter the first reading pattern (uORF1), which it translates, and upon reaching the stop triplet, it encounters a permissive termination, causing the large subunit to dissociate, but the small subunit remains bound to the mRNA.
The small subunit then reaches the second reading pattern (uORF4), but since the concentration of active eIF2 is high, it has time to bind to the small subunit before it starts reading uORF4, allowing the complete ribosome to form and translate uORF4.
In conditions of amino acid scarcity, the concentration of active eIF2 is low, and the small subunit reaches the first reading pattern (uORF1) and encounters a permissive termination, but since the concentration of active eIF2 is low, the small subunit continues scanning the mRNA and bypasses the non-permissive termination of uORF4, allowing it to reach the GCN4 sequence and translate it.

uORFs and Their Effects on Translation

uORFs are a trap for ribosomes, making them start translating from the uORF and getting trapped, and never reaching the real coding sequence.
The presence of a uORF is a regulatory mechanism that determines the translation and/or stability of the mRNA.

5.2 Alternative Translation Initiations

Regulation of protein quantity in the cell can occur through alternative translation initiations, such as skipping the uORF or using alternative AUGs.
Alternative ORFs (aORFs) can produce truncated proteins, and the cell can combine alternative translation initiations and produce proteins with variable N-termini.

5.3 5'-UTR: Autogenous Regulation

The 5'-UTR region has various regulatory elements, such as IRES sequences, uORF sequences, and sequences that form structures recognizable by proteins related to translation regulation.
There are autogenous regulatory mechanisms, similar to those in prokaryotes, that control the translation of certain proteins based on whether they are in excess or deficiency.

5.4 3'-UTR: Activation via PABP

The 3'-UTR region has structures recognizable by proteins related to mRNA stability, and binding sites for miRNAs, which can regulate translation initiation.
The polyA tail in the 3'-UTR stimulates translation by being a binding site for PABP, which is an stimulator of the formation of the cap-binding complex, making it easier to initiate translation.

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Description

Learn about the role of mRNA sequence in the 3 stages of translation, including initiation, elongation, and termination. Understand how uORFs and 5'-UTR sequences regulate translation and how alternative translation initiations can occur.