Glowing RNA strands within red blood cell.

Decoding Red Blood Cell Development: The Unexpected Role of Non-Coding RNAs

Jordan Keane in Science & Nature September 2025 • 3 min read.

"Uncover how long non-coding RNAs (lncRNAs) orchestrate the complex process of erythropoiesis, influencing everything from cell proliferation to terminal maturation."

Erythropoiesis, the creation of red blood cells, is fundamental to life. It's a tightly controlled process where pluripotent hematopoietic stem cells commit to becoming erythrocytes, the oxygen-carrying red blood cells (RBCs) that keep us going. This complex journey occurs in stages, from the yolk sac in early development to the fetal liver and, finally, the bone marrow.

For years, scientists have focused on transcription factors and growth signals as the primary regulators of erythropoiesis. However, recent discoveries have illuminated the critical role of another class of molecules: long non-coding RNAs (lncRNAs). These molecules, unlike messenger RNAs, don't code for proteins, but instead act as regulators of gene expression.

This article explores the fascinating world of lncRNAs and their involvement in erythropoiesis. We'll explore how they influence cell fate, proliferation, and the final maturation steps that give rise to functional red blood cells.

LncRNAs: The Unsung Heroes of Red Blood Cell Development

Glowing RNA strands within red blood cell.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides that don't translate into proteins. Initially overlooked, they are now recognized as key players in a variety of biological processes, including development and disease. Their diverse mechanisms of action allow them to fine-tune gene expression with remarkable precision.

Unlike microRNAs that operate post-transcriptionally, lncRNAs exert their influence in a multitude of ways. They can act:

In cis: Affecting the expression of nearby genes on the same chromosome.
In trans: Regulating genes located far away, even on different chromosomes.
As scaffolds: Providing a platform for the assembly of protein complexes.
As decoys: Titrating away proteins from their targets.
As guides: Directing proteins to specific locations in the genome.

The involvement of lncRNAs in erythropoiesis is becoming increasingly clear, with research demonstrating their impact at various stages of red blood cell development. Many lncRNAs in erythroid cells are regulated by erythroid-specific transcription factors and are expressed in a developmental stage-specific manner, demonstrating their importance in erythroid differentiation and proliferation.

The Future of LncRNA Research in Blood Disorders

The discovery of lncRNAs' role in erythropoiesis opens new avenues for understanding and treating blood disorders. As research progresses, we may find ways to target these molecules to improve red blood cell production in conditions like anemia or to prevent abnormal blood cell growth in diseases like leukemia. The story of lncRNAs is just beginning, and their potential to revolutionize medicine is immense.

About this Article -

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Everything You Need To Know

What is erythropoiesis and why is it important?

Erythropoiesis is the process by which red blood cells (RBCs) are created. This complex process is fundamental to life because RBCs are responsible for carrying oxygen throughout the body. It involves a series of stages where pluripotent hematopoietic stem cells commit to becoming erythrocytes, the oxygen-carrying red blood cells. The journey begins in early development in the yolk sac, then shifts to the fetal liver, and finally takes place in the bone marrow. Understanding this process is key to addressing blood disorders.

How do long non-coding RNAs (lncRNAs) influence the development of red blood cells?

Long non-coding RNAs (lncRNAs) play a critical role in red blood cell development by regulating gene expression. Unlike messenger RNAs, lncRNAs do not code for proteins, but instead act as regulators. They influence cell fate, proliferation, and the final maturation steps that give rise to functional red blood cells. LncRNAs can affect the expression of nearby genes (in cis), regulate genes far away (in trans), act as scaffolds for protein complexes, act as decoys, or guide proteins to specific locations in the genome.

What are the different ways lncRNAs function in the context of red blood cell development?

Long non-coding RNAs (lncRNAs) function through multiple mechanisms to influence red blood cell development. They can act 'in cis' by affecting the expression of genes on the same chromosome, or 'in trans' by regulating genes on different chromosomes. LncRNAs can also serve as scaffolds to assemble protein complexes, act as decoys to sequester proteins, or guide proteins to specific locations within the genome. These diverse roles allow lncRNAs to finely tune gene expression during erythropoiesis.

What is the difference between lncRNAs and messenger RNAs (mRNAs)?

The key difference between long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) lies in their function. Messenger RNAs code for proteins, which carry out various cellular functions. In contrast, lncRNAs do not code for proteins. Instead, they act as regulators of gene expression, influencing how genes are turned on or off. This regulatory role of lncRNAs is crucial in processes such as erythropoiesis, where precise control of gene expression is necessary for the development of red blood cells.

How can understanding lncRNAs improve the treatment of blood disorders?

The discovery of the role of long non-coding RNAs (lncRNAs) in erythropoiesis opens new avenues for treating blood disorders. By understanding how lncRNAs influence red blood cell development, researchers can potentially target these molecules to improve red blood cell production in conditions like anemia, or prevent abnormal blood cell growth in diseases like leukemia. This could lead to the development of new therapies that modulate lncRNA activity to treat a variety of blood-related diseases.