biology

Poly(A)-binding protein

Poly(A)-binding protein is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Poly(A)-binding protein rather than just read about it. In short: Poly(A)-binding protein (PAB or PABP) is an RNA-binding protein which triggers the binding of eukaryotic initiation factor 4 complex (eIF4G) directly to the poly(A) tail of mRNA which is 200-250 nucleotides long. The poly(A) tail is located on the 3' end of mRNA and was discovered by Mary Edmonds, who also characterized the poly-A polymerase enzyme that generates the poly(a) tail.

Key takeaways

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Reference excerpt

Poly(A)-binding protein (PAB or PABP) is an RNA-binding protein which triggers the binding of eukaryotic initiation factor 4 complex (eIF4G) directly to the poly(A) tail of mRNA which is 200-250 nucleotides long. The poly(A) tail is located on the 3' end of mRNA and was discovered by Mary Edmonds, who also characterized the poly-A polymerase enzyme that generates the poly(a) tail. The binding protein is also involved in mRNA precursors by helping polyadenylate polymerase add the poly(A) nucleotide tail to the pre-mRNA before translation. The nuclear isoform selectively binds to around 50 nucleotides and stimulates the activity of polyadenylate polymerase by increasing its affinity towards RNA. Poly(A)-binding protein is also present during stages of mRNA metabolism including nonsense-mediated decay and nucleocytoplasmic trafficking. The poly(A)-binding protein may also protect the tail from degradation and regulate mRNA production. Without these two proteins in-tandem, then the poly(A) tail would not be added and the RNA would degrade quickly.

Structure

Cytosolic poly-A binding protein (PABPC) is made up of four RNA recognition motifs (RRMs) and a C-terminal region known as the PABC domain. RRM is the most common motifs for RNA recognition and is usually made up of 90-100 amino acids. Previous solution NMR and X-ray crystallography studies have shown that RRMs are globular domains, each composed of 4 anti-parallel β sheets that are backed by 2 α-helices. The central two β-strands, connected by a short linker, of each RRM forms a trough-like surface that is thought to be responsible for binding to the poly(A) oligonucleotides. The polyadenylate RNA adopts an extended conformation running the length of the molecular trough. Adenine recognition is primarily mediated by contacts with conserved residues found in the RNP motifs of the two RRMs. In vitro studies have shown the binding affinities to be on the order of 2-7nM, while affinity for poly(U), poly(G), and poly(C) were reportedly lower or undetectable in comparison. This shows that the poly(A)-binding protein is specific to poly(A) oligonucleotides and not others. Since the two central β-strands are used for poly(A) oligonucleotide binding, the other face of the protein is free for protein-protein interactions. The PABC domain is approximately 75 amino acids and consists of 4 or 5 α-helices depending on the organism – human PABCs have 5, while yeast has been observed to have 4. This domain does not contact RNA, and instead, it recognizes 15 residues sequences that are a part of the PABP interaction motif (PAM-2) found on such proteins as eukaryotic translation termination factor (eRF3) and PABP interacting proteins 1 and 2 (PAIP 1, PAIP2). The structure of human poly(A)-binding protein found in the nucleus (PABPN1) has yet to be well determined but it has been shown to contain a single RRM domain and an arginine rich carboxy terminal domain. They are thought to be structurally and functionally different from poly-A binding proteins found in the cytosol.

Expression and binding The expression of mammalian poly(A)-binding protein is regulated at the translational level by a feed-back mechanism: the mRNA encoding PABP contains in its 5' UTR an A-rich sequence which binds poly(A)-binding protein. This leads to autoregulatory repression of translation of PABP. The cytosolic isoform of eukaryotic poly(A)-binding protein binds to the initiation factor eIF4G via its C-terminal domain. eIF4G is a component of the eIF4F complex, containing eIF4E, another initiation factor bound to the 5' cap on the 5' end of mRNA. This binding forms the characteristic loop structure of eukaryotic protein synthesis. Poly(A)-binding proteins in the cytosol compete for the eIF4G binding sites. This interaction enhances both the affinity of eIF4E for the cap structure and PABP1 for poly(A), effectively locking proteins onto both ends of the mRNA. As a result, this association may in part underlie the ability of PABP1 to promote small ribosomal (40S) subunit recruitment, which is aided by the interaction between eIF4G and eIF3. Poly(A)-binding protein has also been shown to interact with a termination factor (eRF3). The eRF3/PABP1 interaction may promote recycling of terminating ribosomes from the 3' to 5' end, facilitating multiple rounds of initiation on an mRNA. Alternatively, it may link translation to mRNA decay, as eRF3 appears to interfere with the ability of PABP1 to multimerise/form on poly(A), potentially leading to PABP1 dissociation, deadenylation and, ultimately, turnover.

Rotavirus NSP3

Rotavirus RNA-binding protein NSP3 interacts with eIF4GI and evicts the poly(A) binding protein from eIF4F. NSP3A by taking the place of PABP on eIF4GI, is responsible for the shut-off of cellular protein synthesis. Rotavirus mRNAs terminate a 3’ GACC motif that is recognized by the viral protein NSP3. This is the location where NSP3 competes with poly(A)-binding protein for eIF4G binding. Once rotavirus infection occurs viral GACC-tailed mRNAs are translated while the poly(A)-tailed mRNA is severely impaired. In infected cells, there have been high magnitudes of both translation induction (GACC-tailed mRNA) and reduction (poly(A)-tailed mRNA) both dependent on the rotavirus strain. These data suggest that NSP3 is a translational surrogate of the PABP-poly(A) complex; therefore, it cannot by itself be responsible for inhibiting the translation of host poly(A)-tailed mRNAs upon rotavirus infection. PABP-C1 evicted from eIF4G by NSP3 accumulates in the nucleus of rotavirus-infected cells. This eviction process requires rotavirus NSP3, eIF4G, and RoXaN. To better understand the interaction, modeling of the NSP3-RoXaN complex, demonstrates mutations in NSP3 interrupt this complex without compromising NSP3 interaction with eIF4G. The nuclear localization of PABP-C1 is dependent on the capacity of NSP3 to interact with eIF4G and also requires the interaction of NSP3 with a specific region in RoXaN, the leucine- and aspartic acid-rich (LD) domain. RoXaN is identified as a cellular partner of NSP3 involved in the nucleocytoplasmic localization of PABP-C1.

Associated diseases

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Illustrations

Worked examples

Example 1 — a first encounter with Poly(A)-binding protein

Start with the simplest possible case. Write down what Poly(A)-binding protein claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Poly(A)-binding protein before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Poly(A)-binding protein ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Poly(A)-binding protein

In research: Poly(A)-binding protein appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Poly(A)-binding protein in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Poly(A)-binding protein is common in secondary-school and first-year university syllabi. It links to neighbouring topics RNA-binding proteins, so understanding it makes those chapters shorter.
In everyday life: Look for Poly(A)-binding protein outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Poly(A)-binding protein in 20 minutes

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Frequently asked questions

What is Poly(A)-binding protein in simple terms?

Why does Poly(A)-binding protein matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Poly(A)-binding protein?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Poly(A)-binding protein.