RNA fusion refers to a biological event where two distinct genes, normally located separately, become joined together. This joining results in a single, hybrid RNA molecule with novel characteristics. The formation of these unique RNA molecules can significantly alter cellular processes, creating new instructions for the cell.
Understanding RNA Fusions
Genes serve as fundamental blueprints for creating proteins, which carry out most of the work in cells. RNA acts as an intermediary molecule, translating genetic information from DNA into protein. An RNA fusion occurs when segments from two different genes are transcribed together, forming one continuous RNA transcript. This means the cell generates a single, combined RNA instead of two separate molecules.
This phenomenon often originates at the DNA level, where two genes physically merge to form a “fusion gene.” This DNA alteration leads to a fused RNA molecule carrying genetic instructions from both original genes, potentially creating a new, combined protein.
How RNA Fusions Arise
RNA fusions primarily arise from alterations in the cell’s DNA, often involving large-scale chromosomal rearrangements. These include translocations (parts of chromosomes swap places), deletions (segments are lost), or inversions (a segment’s orientation is reversed). Such rearrangements bring previously separate genes into close proximity, leading to their transcription as a single, continuous RNA molecule.
These genetic errors often occur during cellular processes such as cell division or DNA repair. RNA fusions can also form through splicing mechanisms like trans-splicing (joining exons from two different RNA transcripts) or cis-splicing (involving adjacent genes on the same DNA strand). Both processes can result in a fused RNA even without a direct DNA gene fusion.
Cellular Consequences of RNA Fusions
When an RNA fusion molecule is formed, it can be translated into a hybrid protein within the cell. This new protein often possesses altered functions or entirely new properties compared to the original, separate proteins. For instance, a fusion protein might gain constant activity, leading to uncontrolled signaling pathways.
Such altered functions can disrupt normal cellular behavior and regulation. This disruption might manifest as uncontrolled cell growth, a characteristic of cancerous cells, or resistance to the cell’s natural control mechanisms. In some instances, fusion RNAs may even function as noncoding RNAs, influencing cellular processes without being translated into a protein.
RNA Fusions in Disease and Medicine
RNA fusions play a role in various diseases, particularly cancer, where they drive tumor development. Specific RNA fusions are genetic alterations in many cancers, including leukemias, lung cancers, sarcomas, and prostate cancers. Examples include BCR-ABL1 in chronic myelogenous leukemia (CML), EML4-ALK in lung cancers, and TMPRSS2-ERG in prostate cancer. These fusion proteins can lead to uncontrolled cell proliferation and survival, contributing to tumor formation.
Detecting specific RNA fusions serves as a diagnostic biomarker for identifying diseases or cancer subtypes. This molecular information aids in accurate diagnosis and offers insights into the disease’s probable course. Modern techniques like RNA sequencing (RNA-Seq) have improved the ability to identify fusion events, offering a more accurate and sensitive diagnostic approach.
Since these abnormal fusion proteins contribute to disease progression, they are targets for precision medicine. Researchers can develop drugs to inhibit the activity of these fusion proteins. This targeted approach aims to treat the disease by neutralizing the specific molecular abnormality, often resulting in more precise therapies with fewer side effects than traditional treatments.