What Are RNA Fragments and What Are Their Functions?

Ribonucleic acid (RNA) is a molecule that carries instructions from DNA to control the synthesis of proteins. While large RNA molecules like messenger RNA (mRNA) are known for this role, cells also contain many RNA fragments. These smaller pieces are not cellular debris but are distinct molecules derived from larger RNA precursors. These fragments are now understood to be active participants in a wide range of cellular activities, opening new avenues for understanding biological regulation.

How RNA Fragments Are Formed

The generation of RNA fragments is a controlled process, driven by specific enzymes that cleave larger RNA molecules at precise locations. This enzymatic activity is a part of normal cellular function. For instance, enzymes named Dicer and Drosha act like molecular scissors, cutting specific RNA structures to produce functional units.

Beyond this targeted production, RNA fragments also arise from broader RNA degradation pathways. Cells have systems for breaking down RNA molecules that are no longer needed or have become damaged. While much of this material is recycled, some resulting fragments can be repurposed. This fragmentation can increase in response to cellular stress, such as exposure to toxins or changes in temperature.

The origin of the parent RNA molecule dictates the type of fragment produced. Different classes of RNA, from protein-coding mRNAs to non-coding transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), can all serve as sources. The specific enzyme involved and the location of the cut are tightly regulated, leading to a diverse population of RNA fragments.

Prominent Types of RNA Fragments

MicroRNAs (miRNAs) are among the most studied RNA fragments. These short, single-stranded molecules are about 22 nucleotides long and originate from longer RNA precursors that form a hairpin loop. The enzymes Drosha and Dicer process these precursors into mature miRNAs, which are regulators of gene expression in most eukaryotic organisms.

Small interfering RNAs (siRNAs) are another class of fragments similar in size to miRNAs. They are derived from long, double-stranded RNA molecules, which can originate from viral infections or an organism’s own genome. The Dicer enzyme cuts these long molecules into siRNAs, which are part of a cellular defense mechanism called RNA interference.

Piwi-interacting RNAs (piRNAs) are slightly longer fragments, around 26 to 31 nucleotides, found mainly in animal germline cells (sperm and eggs). PiRNAs function with Piwi proteins to maintain the integrity of genetic information passed to the next generation.

Cells also produce fragments from transfer RNAs, known as tRNA-derived RNA fragments (tRFs) and tRNA halves (tiRNAs). These are generated from tRNA molecules by specific enzymes, and their production can increase during cellular stress. Similarly, ribosomal RNA (rRNA) can be processed into functional rRNA-derived fragments (rRFs).

Cellular Functions of RNA Fragments

A primary function of many RNA fragments is regulating gene expression. MiRNAs and siRNAs are known for silencing genes after transcription. They bind to complementary sequences on target mRNA molecules, which can lead to the mRNA’s destruction or block it from being translated into a protein, effectively turning the gene off.

Some RNA fragments specialize in genome defense. PiRNAs and their Piwi protein partners protect the genome of germline cells from transposable elements, or “jumping genes.” These DNA sequences can move within the genome and cause harmful mutations. PiRNAs guide Piwi proteins to neutralize the RNAs from these elements, preventing them from spreading.

Other fragments modulate protein synthesis. For example, certain tRFs can interfere with the ribosome, the machine that builds proteins. By doing so, they can inhibit or enhance the translation of specific mRNAs. This function is particularly useful during the cellular stress response, where rapid changes in protein synthesis are required.

RNA fragments also participate in intercellular communication. They can be packaged into extracellular vesicles, which are released by one cell and taken up by another, transferring regulatory information between distant parts of an organism. The presence of specific fragments in these vesicles can signal changes in cellular state, like the onset of disease.

RNA Fragments in Research and Medicine

RNA fragments are tools for scientific research. Scientists use RNA interference by introducing custom-designed siRNAs into cells to selectively turn off a gene they wish to study. This technique, gene knockdown, allows researchers to investigate a gene’s function by observing what happens when its product is absent.

In medicine, RNA fragments are emerging as biomarkers for diagnosing and monitoring diseases. They are stable and found in bodily fluids like blood and urine, so specific fragments can indicate conditions like cancer or neurodegenerative disorders. For instance, altered levels of certain miRNAs in the blood have been linked to the presence of tumors.

The regulatory power of RNA fragments is also being used for therapeutic purposes. Drugs based on siRNA technology are developed to treat genetic disorders by silencing the genes causing the illness. For diseases caused by an miRNA deficiency, “miRNA mimics” can be introduced to restore its function. This field of RNA-based medicine offers new ways to treat difficult conditions.