RNA interference (RNAi): by Nature Video

Summary

The animation delves into RNA interference (RNAi), a gene regulation mechanism used by organisms and a potential therapeutic tool. It explains the roles of small interfering RNAs (siRNAs) and microRNAs (miRNAs) in silencing gene expression. siRNAs, derived from double-stranded RNA, guide the RNA-induced silencing complex (RISC) to cleave specific mRNAs. miRNAs, processed from nuclear RNA, can target hundreds of mRNAs through partial base pairing, leading to mRNA degradation or translation inhibition. The importance of these small RNAs in various biological processes is highlighted.

Takeaways

• 🔬 RNA interference (RNAi) is a mechanism used by many organisms to control gene expression and has potential therapeutic applications.
• 🧬 RNAi involves two key types of RNA molecules: small interfering RNAs (siRNAs) and micro RNAs (miRNAs).
• 🌟 Eukaryotic cells use sophisticated mechanisms, including RNAi, to precisely control gene expression within the cell.
• 🧐 siRNAs are derived from longer double-stranded RNAs and can be used to manipulate gene expression in the laboratory.
• 🌱 miRNAs originate from RNAs transcribed in the nucleus, processed, and then exported to the cytoplasm as double-stranded precursors.
• ✂️ Dicer, an endoribonuclease, processes siRNAs and miRNAs into short segments, typically 21 nucleotides long.
• 🔒 siRNAs and miRNAs bind to argonaut proteins to form the RNA-induced silencing complex (RISC), which mediates gene silencing.
• 🎯 siRNAs guide RISC to specific mRNAs through perfect base pairing, leading to mRNA cleavage and degradation.
• 🌐 miRNAs guide RISC less precisely, with only a portion (the seed) pairing with target mRNAs, allowing them to regulate multiple genes.
• 🌿 Argonaut proteins and their small regulatory RNA cofactors are found across various organisms, highlighting their broad biological significance.

Q & A

What is RNA interference (RNAi)?

RNA interference (RNAi) is a mechanism used by organisms to control gene expression through small RNA molecules that direct gene silencing.

How does RNAi work in eukaryotic cells?

In eukaryotic cells, RNAi involves small RNA molecules that bind to specific messenger RNAs (mRNAs) and either degrade them or inhibit their translation into proteins.

What are the two important types of RNA molecules involved in RNAi?

The two important types of RNA molecules involved in RNAi are small interfering RNAs (siRNAs) and micro RNAs (miRNAs).

Where do siRNAs originate from?

siRNAs are derived from longer double-stranded RNAs that can be produced within the cell or introduced experimentally.

How are siRNAs used in the laboratory?

In the laboratory, siRNAs are used to manipulate gene expression by introducing them into cells to specifically target and degrade mRNAs of interest.

What is the role of Dicer in RNAi?

Dicer is an endoribonuclease protein that processes double-stranded precursors of siRNAs and miRNAs into short segments, typically about 21 nucleotides long.

What is the RNA-induced silencing complex (RISC) and how does it function?

The RNA-induced silencing complex (RISC) is a complex formed by the binding of short double-stranded RNA to an argonaut protein. It guides the complex to specific mRNAs for degradation or translation inhibition.

How does the guide strand of RNA within RISC determine its target?

The guide strand within RISC determines its target through base pairing with the mRNA, with siRNAs often having perfect complementarity to their target sites.

What is the difference between siRNAs and miRNAs in terms of their targeting mechanism?

siRNAs have perfect complementarity to their target mRNAs, leading to mRNA cleavage and degradation, while miRNAs only partially pair with their targets, usually through a region called the 'seed,' allowing them to target a broader range of mRNAs.

What are the potential therapeutic applications of RNAi?

RNAi has potential therapeutic applications as it can be used to silence specific genes that are involved in disease processes, offering a targeted approach to treatment.

In which organisms are argonauts and their small regulatory RNA cofactors found?

Argonauts and their small regulatory RNA cofactors are found in plants, animals, fungi, and some bacteria, highlighting their widespread importance in biological processes.

Outlines

00:00

🧬 RNA Interference (RNAi) Overview

This paragraph introduces RNA interference (RNAi), a mechanism used by organisms to control gene expression. It highlights the role of small interfering RNAs (siRNAs) and micro RNAs (miRNAs) in this process. The script explains how genes are transcribed into messenger RNA (mRNA), which is then translated into proteins. The focus is on how small RNA molecules can direct gene silencing within the cell, either by degrading the mRNA or inhibiting its translation. The paragraph also discusses the origin of siRNAs and miRNAs, their processing, and how they form the RNA-induced silencing complex (RISC) to regulate gene expression.

Keywords

💡RNA interference (RNAi)

RNA interference, or RNAi, is a biological process where RNA molecules play a role in the regulation of gene expression. It's a mechanism that cells use to silence or inhibit the activity of specific genes. In the context of the video, RNAi is highlighted as a rapidly advancing field of study that has potential therapeutic applications. The video emphasizes its importance in controlling genes and its use as a tool in research.

💡small interfering RNAs (siRNAs)

Small interfering RNAs, or siRNAs, are a type of small RNA molecule that is derived from longer double-stranded RNAs. They are used in the RNAi pathway to guide the degradation of specific messenger RNAs (mRNAs), thereby silencing the expression of particular genes. The video explains that siRNAs are either produced within the cell or introduced experimentally and are crucial for manipulating gene expression.

💡micro RNAs (miRNAs)

Micro RNAs, or miRNAs, are another class of small non-coding RNA molecules that are involved in post-transcriptional regulation of genes. They originate from RNAs transcribed in the nucleus, processed, and then exported to the cytoplasm. The video describes how miRNAs, once in the cytoplasm, can guide the RNA-induced silencing complex (RISC) to specific mRNAs, leading to gene silencing either by degradation or translation inhibition.

💡Dicer

Dicer is an endoribonuclease protein that plays a pivotal role in the RNAi pathway. It is responsible for cleaving double-stranded RNA into short segments, which are typically about 21 nucleotides long. In the video, Dicer is mentioned as a key component that processes both siRNAs and miRNAs, making them ready to be incorporated into the RISC complex.

💡RNA-induced silencing complex (RISC)

The RNA-induced silencing complex, or RISC, is a multi-protein complex that includes an argonaut protein and a small RNA molecule, either an siRNA or a miRNA. RISC is central to the RNAi mechanism as it binds to specific mRNAs, leading to their cleavage and degradation. The video explains that RISC is guided by the 'guide strand' of the small RNA to its target mRNA through base pairing.

💡messenger RNA (mRNA)

Messenger RNA, or mRNA, is a single-stranded RNA molecule that is transcribed from a DNA template and carries genetic information from the nucleus to the cytoplasm. In the video, mRNA is described as the molecule that is translated by ribosomes into proteins. However, it can also be targeted by RNAi mechanisms, such as siRNAs and miRNAs, which can lead to its degradation or inhibit its translation.

💡gene expression

Gene expression refers to the process by which information from a gene is used in the synthesis of a functional gene product, typically a protein. The video discusses how RNAi mechanisms, including siRNAs and miRNAs, are used to control gene expression by silencing specific genes, which is crucial for various biological processes and can be harnessed for therapeutic purposes.

💡gene silencing

Gene silencing is the process by which the expression of a gene is inhibited, either temporarily or permanently. In the video, gene silencing is a key theme, as it is the primary outcome of the RNAi pathway. This can occur through the degradation of mRNA by RISC or by inhibiting the translation of mRNA into proteins, which are mediated by siRNAs and miRNAs.

💡base pairing

Base pairing is a fundamental principle in molecular biology where two complementary strands of nucleic acids (DNA or RNA) pair up through hydrogen bonds between their nitrogenous bases. The video explains that the specificity of siRNAs in directing RISC to its target mRNA is determined by base pairing, which ensures that only the intended mRNA is targeted for degradation.

💡translation

Translation is the process by which the genetic information encoded in mRNA is used to synthesize proteins. The video describes how ribosomes in the cytoplasm facilitate the translation of mRNA into polypeptide chains. However, this process can be inhibited by miRNAs, which can lead to gene silencing without the need for mRNA degradation.

💡seed

In the context of miRNAs, the 'seed' refers to a specific region, usually around 6-8 nucleotides, at the 5' end of the miRNA that is crucial for base pairing with the target mRNA. The video explains that the seed sequence allows for less precise matching compared to siRNAs, enabling a single miRNA to potentially target hundreds of different mRNAs.

Highlights

Scientists have made rapid progress in understanding RNA interference (RNAi), which controls gene expression in organisms.

RNAi is a tool in the laboratory and may be used as a therapy in the future.

RNAi involves two important types of RNA: small interfering RNAs (siRNAs) and microRNAs (miRNAs).

Eukaryotic cells have sophisticated mechanisms to control gene expression, including small RNA molecules for gene silencing.

RNA polymerase II transcribes most protein-encoding genes in the nucleus, which are processed into mature messenger RNA (mRNA).

In the cytoplasm, ribosomes translate mRNA into polypeptide chains that fold into functional proteins.

siRNAs come from longer double-stranded RNAs, produced in the cell or delivered experimentally, to manipulate gene expression.

MicroRNAs are another type of small RNA, transcribed in the nucleus and exported as double-stranded precursor miRNAs.

Both siRNAs and miRNAs bind to Dicer, an endoribonuclease, which cuts the RNA into short segments.

siRNAs and miRNAs are approximately 21 nucleotides long and bind to an Argonaute protein.

The guide strand of the RNA remains bound to Argonaute, forming the RNA-induced silencing complex (RISC).

siRNAs guide RISC to target mRNA through precise base pairing, leading to the degradation of the target mRNA.

MicroRNAs guide RISC to target mRNA with partial base pairing, allowing them to target hundreds of endogenous mRNAs.

MicroRNA targeting can lead to mRNA degradation or inhibition of translation.

Argonaute proteins and their small RNA partners are found in plants, animals, fungi, and some bacteria, influencing numerous biological processes.

Transcripts

Scientists have been making rapid progress in understanding RNA interference or RNAi.

Many organisms use RNAi to control genes, and it can also be used as a tool in the laboratory,

and in future, perhaps, as a therapy.

This animation will introduce you to the principles of RNAi

involving two important types of RNA molecule – small interfering RNAs and micro RNAs.

Eukaryotic cells have many sophisticated ways of controlling gene expression.

In the complex environment of a cell, these mechanisms need to be precisely targeted.

There's a group of mechanisms that use small RNA molecules to direct gene silencing. This is called RNAi.

Inside the nucleus, most genes that encode proteins are transcribed by RNA polymerase II.

The primary RNA transcript is processed by splicing and forms a mature messenger RNA,

sometimes called mRNA.

The messenger RNA is then exported from the nucleus into the cytoplasm.

Here, ribosomes catalyse translation of the messenger RNA to form polypeptide chains that fold into proteins.

But this is also where some small RNA molecules can have their silencing effects.

There are several types of regulatory small RNA.

Small interfering RNAs, known as siRNAs, are derived from longer double-stranded RNAs

that are either produced in the cell itself or are delivered into cells experimentally.

The introduction of siRNAs or double-stranded RNA is widely used to manipulate gene expression.

MicroRNAs are another type of small RNA.

Most microRNAs come from RNAs that are transcribed in the nucleus, which then fold and are processed

before being exported into the cytoplasm as double-stranded precursor microRNAs.

The double-stranded precursors of microRNAs and siRNAS bind to Dicer,

which is an endoribonuclease protein that cuts the RNA into short segments.

Most siRNAs and microRNAs are approximately 21 nucleotides long.

The short double-stranded RNA then binds an argonaut protein.

One strand of the RNA is selected and remains bound to argonaut.

This is called the guide strand.

The combination of the RNA and argonaut, along with other proteins,

is called the RNA-induced silencing complex or RISC.

siRNAs direct RISC to bind to specific messenger RNAs.

The targeting is precise because it's determined by a base pairing

between the siRNA and the target messenger RNA.

siRNAs often have perfect complementarity to their target sites.

Once bound, argonaut catalyses cleavage of the messenger RNA, which will then be degraded.

MicroRNAs also guide RISC to messenger RNAs.

Usually, only part of a microRNA, known as the seed, pairs with a target messenger RNA.

This imprecise matching allows microRNAs to target hundreds of endogenous messenger RNAs.

Targeting via microRNA can lead to messenger RNAs being degraded or translation being inhibited.

Argonauts and their small regulatory RNA code factors are found in plants, animals, fungi, and some bacteria,

and their importance in a multitude of biological processes, and as tools, continues to be revealed.