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Negative elongation factor

Negative elongation factor 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 Negative elongation factor rather than just read about it. In short: In molecular biology, the NELF (negative elongation factor) is a four-subunit protein complex (NELF-A, NELF-B, NELF-C/NELF-D, and NELF-E) that negatively impacts transcription by RNA polymerase II (Pol II) by pausing about 20–60 nucleotides downstream from the transcription start site (TSS). Structure The NELF has four subunits within its complex which are the following: NELF-A, NELF-B, NELF-C/NELF-D, and NELF-E.

Negative elongation factor — main illustration
Negative elongation factor — illustration

Key takeaways

  • Negative elongation factor belongs to biology; place it in that map before memorising details.
  • Learn the definition first, then one example that makes the definition concrete.
  • Connect Negative elongation factor to a quantity you can measure, compute or draw — that is where exam questions come from.
  • Reproduce the core statement of Negative elongation factor from memory before moving on to harder problems.

Reference excerpt

In molecular biology, the NELF (negative elongation factor) is a four-subunit protein complex (NELF-A, NELF-B, NELF-C/NELF-D, and NELF-E) that negatively impacts transcription by RNA polymerase II (Pol II) by pausing about 20–60 nucleotides downstream from the transcription start site (TSS).

Structure The NELF has four subunits within its complex which are the following: NELF-A, NELF-B, NELF-C/NELF-D, and NELF-E. The NELF-A subunit is encoded by the gene WHSC2 (Wolf-Hirschhorn syndrome candidate 2). Micro-sequencing analysis demonstrated that NELF-B was the protein previously identified as being encoded by the gene COBRA1. It is unknown whether or not NELF-C and NELF-D are peptides resulting from the same mRNA with different translation initiation sites; possibly differing only in an extra 9 amino acids for NELF-C at the N-terminus, or peptides from different mRNAs entirely. A single NELF complex consists of either NELF-C or NELF-D, but not both. NELF-E is also known as RDBP.

Function and Interactions NELF is located in the nucleus. NELF binds in a stable complex with DSIF (5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB)-sensitivity inducing factor) and RNA polymerase II together, but not with either alone. Due to its role in transcription, NELF is also a key player in the negative function of DSIF. NELF also works with DSIF to inhibit the speed of Pol II during the elongation phase in transcription. In D. melanogaster, the HSP70 gene is affected by NELF and DSIF through the induction of promoter proximal pausing. It is thought that NELF arose to assist DSIF by amplifying its negative effects in order to increase gene expression control. P-TEFb (positive transcription elongation factor b) inhibits the effect of NELF and DSIF on Pol II elongation, via its phosphorylation of serine-2 of the C-terminal domain of Pol II, and the SPT5 subunit of DSIF, causing dissociation of NELF.

Another mechanism, interaction of enhancer RNA with NELF, causes dissociation of NELF from RNA polymerase II, resulting in productive elongation of mRNA, as studied in two immediate early genes. However, many mechanisms by which NELF and DSIF operate remain unclear. NELF homologues exist in some metazoans (e.g. insects and vertebrates) but have not been found in plants, yeast, or nematodes (worms). Interactions by subunit:

NELF-A: Pol II complex. NELF-B: KIAA1191, NELF-E, and an early sequence of BRCA1. NELF-C/D: ARAF1, PCF11, and KAT8. NELF-E: NELF-B and HIV TAR RNA. NELF undergoes Phase separation in vitro and Condensation in vivo

Clinical Significance The NELF complex is also possibly a player in the enlistment of gene PCF11 to the stopped Pol II in HIV-1 latency. NELF-A may play a role in the phenotype of Wolf-Hirschhorn syndrome (WHS) as it is mapped to the critical area of deletion on the short arm of chromosome 4. Pol II pausing controlled by NELF is a key source of R-loop aggregation in mammary epithelial cells that are BRCA1-deficient, which could ultimately lead to tumorigenesis.

References

Illustrations

Negative elongation factor: Protein structure of the E subunit of the negative elongation factor (NELF-E).
Protein structure of the E subunit of the negative elongation factor (NELF-E).
Negative elongation factor: Regulatory elements, including Negative elongation factor (NELF) and enhancer RNA (eRNA) control transcription of a gene into messenger RNA in metazoans (animals). An active enhancer regulatory region of DNA is enabled to interact with the promoter DNA region of its target gene by the formation of a chromosome loop. This can initiate messenger RNA (mRNA) synthesis by RNA polymerase II (RNAP II) bound to the promoter at the transcription start site of the gene. The loop is stabilized by one architectural protein anchored to the enhancer and one anchored to the promoter and these proteins are joined to form a dimer (red zigzags). Specific regulatory transcription factors bind to DNA sequence motifs on the enhancer. General transcription factors bind to the promoter. When a transcription factor is activated by a signal (here indicated as phosphorylation shown by a small red star on a transcription factor on the enhancer) the enhancer is activated and can now activate its target promoter. The active enhancer is transcribed on each strand of DNA in opposite directions by bound RNAP IIs. Mediator (a complex consisting of about 26 proteins in an interacting structure) communicates regulatory signals from the enhancer DNA-bound transcription factors to the promoter. NELF, in complex with DSIF and RNAP II, can pause transcription. Interaction of eRNA with NELF may release NELF and allow productive elongation of mRNA.
Regulatory elements, including Negative elongation factor (NELF) and enhancer RNA (eRNA) control transcription of a gene into messenger RNA in metazoans (animals). An active enhancer regulatory region of DNA is enabled to interact with the promoter DNA region of its target gene by the formation of a chromosome loop. This can initiate messenger RNA (mRNA) synthesis by RNA polymerase II (RNAP II) bound to the promoter at the transcription start site of the gene. The loop is stabilized by one architectural protein anchored to the enhancer and one anchored to the promoter and these proteins are joined to form a dimer (red zigzags). Specific regulatory transcription factors bind to DNA sequence motifs on the enhancer. General transcription factors bind to the promoter. When a transcription factor is activated by a signal (here indicated as phosphorylation shown by a small red star on a transcription factor on the enhancer) the enhancer is activated and can now activate its target promoter. The active enhancer is transcribed on each strand of DNA in opposite directions by bound RNAP IIs. Mediator (a complex consisting of about 26 proteins in an interacting structure) communicates regulatory signals from the enhancer DNA-bound transcription factors to the promoter. NELF, in complex with DSIF and RNAP II, can pause transcription. Interaction of eRNA with NELF may release NELF and allow productive elongation of mRNA.

Worked examples

Example 1 — a first encounter with Negative elongation factor

Start with the simplest possible case. Write down what Negative elongation factor 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 Negative elongation factor 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 Negative elongation factor 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 Negative elongation factor

In research
Negative elongation factor 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 Negative elongation factor 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
Negative elongation factor is common in secondary-school and first-year university syllabi. It links to neighbouring topics Protein complexes, Transcription factors, so understanding it makes those chapters shorter.
In everyday life
Look for Negative elongation factor 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 Negative elongation factor in 20 minutes

  1. Read the reference excerpt below once, without taking notes.
  2. Close the page and write down what Negative elongation factor means in your own words.
  3. Compare your version with the excerpt and mark what you missed.
  4. Work through the three examples above with pen and paper.
  5. Explain Negative elongation factor out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Negative elongation factor in simple terms?

In molecular biology, the NELF (negative elongation factor) is a four-subunit protein complex (NELF-A, NELF-B, NELF-C/NELF-D, and NELF-E) that negatively impacts transcription by RNA polymerase II (Pol II) by pausing about 20–60 nucleotides downstream from the transcription start site (TSS). Struct…

Why does Negative elongation factor 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 Negative elongation factor?

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 Negative elongation factor.

Tags

  • Protein complexes
  • Transcription factors

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