The Encore of the Central Dogma: ncRNA Takes the Stage and Redefines the Script

-

DNAs Francis Cricks “Central Dogma”


ncRNA “rewrites” this model

The Encore of the Central Dogma: ncRNA Takes the Stage and Redefines the Script 

The once-sacrosanct central dogma of molecular biology, a rigid linear narrative of DNA dictating RNA's transcription, RNA dictating protein translation, now pulsates with the rhythm of a far more intricate composition. Non-coding RNAs (ncRNAs)(Junk DNA), once relegated to the cellular shadows as mere byproducts, have emerged as the enigmatic maestros, wielding a subtle yet transformative baton over the very flow of genetic information. This essay delves into the diverse repertoire of ncRNA, illuminating its profound impact on the central dogma's encore performance, a performance marked by exquisite choreography and profound consequences.

Beyond the familiar realm of protein-coding genes, long non-coding RNAs (lncRNAs) like HOTAIR and HOTTIP pirouette in the transcriptional wings. Their silencing melodies cast a hush over target genes, their voices fading into the cellular backdrop, while their activating arias amplify their expression, raising their volume in the genetic symphony. This pre-emptive regulation sets the stage for the finely tuned post-transcriptional drama conducted by microRNAs (miRNAs). Imagine these nimble molecules as molecular censors, scanning messenger RNA (mRNA) for complementary targets with the precision of a seasoned ballerina. A perfect match ignites a cascade of consequences. The mRNA might be swiftly degraded, its silenced melody fading into the cellular abyss. Or, it might be relegated to the translational shadows, its protein-coding potential repressed, a muted whisper in the gene expression symphony. This post-transcriptional control allows for exquisite fine-tuning, ensuring the right proteins appear at the right time and place, a critical act in maintaining cellular harmony. For instance, miR-21, a miRNA overexpressed in the shadows of cancer, silences genes that orchestrate programmed cell death, allowing tumor cells to proliferate unchecked. Conversely, miRNAs targeting oncogenes act as tumor suppressors, casting a hopeful spotlight on the potential of ncRNA-based cancer therapies.

But the act doesn't end with miRNAs' graceful pirouettes. Enter the alternative splicing troupe, where ncRNA takes on the role of a skilled choreographer. Pre-mRNA, the rough draft of messenger RNA, undergoes a meticulous editing process, with introns (non-coding sequences) excised and exons (coding sequences) meticulously stitched together. This splicing ballet, orchestrated by small nuclear RNAs (snRNAs) and other ncRNA players, allows a single gene to encode a multitude of protein isoforms, each with unique functions, akin to a single melody giving rise to a vibrant symphony. Take the CD45 gene in immune cells: through alternative splicing, it generates a dazzling array of receptor isoforms, each exquisitely attuned to a specific pathogen, a testament to the power of ncRNA to expand the functional repertoire of the cell.

Yet, ncRNA's influence transcends individual genes, shaping the very stage upon which the drama of gene expression unfolds. Long non-coding RNAs like Xist act as set designers, binding to specific chromosomal loci and altering the chromatin landscape. Histone modifiers, recruited by ncRNA, meticulously adjust the accessibility of DNA, effectively raising or lowering the curtains on gene expression. Imagine ncRNAs as epigenetic landscapers, sculpting the chromatin terrain to determine which genes bask in the spotlight of transcription and which remain shrouded in the darkness of repression. This intricate interplay between ncRNA and chromatin organization underpins fundamental biological processes like dosage compensation, where one X chromosome in female cells is silenced by Xist, ensuring equal gene expression with males.

The encore of the central dogma, conducted by the multifaceted orchestra of ncRNA, is a breathtaking performance unlike any other. From the nuanced control of individual genes to the grand orchestration of genome-wide chromatin landscapes, ncRNA exerts a profound influence on cellular function and development. Its dysregulation can lead to the shadows of disease, while its therapeutic potential beckons with the promise of restoring harmony to the symphony of life. As the curtain rises on further ncRNA discoveries, the central dogma's rewrite promises to be even more captivating, a testament to the exquisite dance between genetic information and the enigmatic conductors of the non-coding world.

ncRNA and the Neodarwinian Challenge: A Symphony of Dissent

The once-immutable tenets of neo darwinism, with its linear flow of DNA to RNA to protein, face a powerful counterpoint in the form of non-coding RNAs (ncRNAs). These enigmatic conductors of the cellular orchestra wield a subtle yet transformative baton, shaking the very foundations of the central dogma and offering compelling challenges to the neo darwinian paradigm. Let's explore the discordant notes they introduce:

1. Blurring the lines of inheritance: Neo Darwinism emphasizes DNA as the sole carrier of hereditary information, passed down through generations. However, ncRNAs like lncRNAs have been implicated in epigenetic inheritance, where environmental cues can alter chromatin landscapes and gene expression patterns, potentially even transmitting these changes to offspring. This introduces a level of environmental influence unacknowledged by the strict DNA-centric view of neodarwinism.

2. Deconstructing the linear narrative: The central dogma portrays gene expression as a unidirectional flow, with DNA dictating RNA, which dictates protein. ncRNAs, however, disrupt this linearity. miRNAs can silence mRNA, halting protein translation, while lncRNAs can influence which genes are transcribed in the first place. This intricate interplay introduces feedback loops and regulatory cascades, creating a dynamic web of control that challenges the simplistic model of neodarwinism.

3. Questioning the primacy of selection: Neo Darwinism posits that mutations in DNA, leading to changes in protein function, drive natural selection. However, ncRNAs, particularly miRNAs, can target multiple genes and fine-tune protein levels, potentially masking the effects of individual mutations. This suggests that ncRNA work outside of selection not just on protein sequences, but also on the complex regulatory networks orchestrated by ncRNAs, adding another layer of complexity to the evolutionary landscape.

4. Introducing Lamarckian echoes: Neo Darwinism rejects Lamarckian inheritance, where acquired traits are passed down. However, recent research suggests that environmental cues can influence ncRNA expression patterns, potentially altering gene expression in future generations. This transmission of acquired traits hints at a level of environmental influence on heritable variation, echoing Lamarckian themes in a nuanced way.

5. Expanding the role of chance: Neo Darwinism emphasizes the role of random mutations in driving evolution. However, the vast repertoire of ncRNAs and their intricate regulatory networks introduce another layer of complexity. Stochastic variation in ncRNA expression can lead to phenotypic changes, suggesting that chance might play a bigger role in evolution than previously acknowledged.

In conclusion, ncRNAs' impact on the central dogma is not merely a discordant note; it's a symphony of dissent. They challenge neodarwinism's fundamental tenets by blurring the lines of inheritance, deconstructing the linear narrative, questioning the primacy of selection, introducing Lamarckian echoes, and expanding the role of chance. While not a complete reorchestration, ncRNAs offer a compelling revision of the evolutionary score, urging us to reconsider the melody of life in all its intricate harmony and dissonance.

Remember, the study of ncRNA is still in its nascent stages, and new discoveries are constantly unfolding. As we delve deeper into this fascinating world, the challenges posed to neo darwinism might resonate even louder, potentially leading to a new and more nuanced understanding of evolution itself.

Ref:

Reversing the Central Dogma: RNA-guided control of DNA in epigenetics and genome editing

Long non-coding RNA epigenetics

Epigenetics: An overview of CpG methylation, chromatin remodeling, and regulatory/noncoding RNAs

Epigenetic regulation of gene expression in response to environmental exposures: From bench to model

Comments

Post a Comment

Popular posts from this blog

No, the EES is not just a add on to Neo-Darwinism aka the Modern Synthesis

-
Image
" The summary of the state of affairs on the 150th anniversary of the Origin is somewhat shocking: in the post-genomic era, all major tenets of the Modern Synthesis fthe theory of evolution) are, if not outright overturned replaced by a new and incomparably more complex vision of the key aspects of evolution (EES). So, not to mince words , the Modern Synthesis is gone" -Eugene Koonin, an evolutionary biologist (Cited by over 270,000 evolutionary scientists.) The Extended Evolutionary Synthesis (EES) represents a significant departure from the traditional neo-Darwinian framework, also known as the Modern Synthesis . While both theories aim to explain evolutionary change, they differ fundamentally in their underlying mechanisms and the roles they assign to various biological processes. A crucial point of divergence lies in the interpretation and application of the term " evolutionary ," particularly concerning the incorporation of epigenetic mechanisms....
Read more

Is the random mutational model of evolution on its way out?

-
Image
While the random mutational model of evolution has long been a cornerstone of evolutionary biology, the Extended Evolutionary Synthesis (EES) and the study of epigenetics are challenging its core assumptions. The Random Mutational Model and Its Limitations The traditional view of evolution, often called the Modern Synthesis or neo-Darwinism , emphasizes random genetic mutations as the primary source of variation. Natural selection then acts upon this variation, favoring individuals with advantageous traits. This model has been successful in explaining some evolutionary phenomena, but it also has limitations: It struggles to explain complex adaptations: The idea that complex features like the eye or the immune system arose solely through random mutations seems statistically improbable. It overlooks the role of the environment: The traditional model treats the environment as a selective force, but it doesn't fully consider how organisms can actively respond to and s...
Read more

ERVs and Common Descent: A Reassessment in Light of Recent Findings

-
Image
Endogenous retroviruses (ERVs) have long been considered strong evidence for the common descent of humans and chimpanzees. These remnants of ancient viral infections, embedded in the genomes of both species, were once thought to be non-functional "junk DNA." The premise was that the shared presence of these seemingly random insertions in corresponding genomic locations could best be explained by a shared evolutionary history. However, recent research, such as the "Switching Sides" article published in May 2021, has challenged this assumption by demonstrating that ERVs play a functional role in the development of the human embryo and immune system. This discovery raises questions about the validity of using ERVs as primary evidence for common descent. The Traditional Argument for Common Descent The traditional argument for common descent based on ERVs rests on the following points: Random Insertion: Retroviral insertions are thought to occur randomly in...
Read more