Overview of Research Achievements in The Field of

RNA Molecular Biology Research

In the last post, we have introduced some of the research achievements in the RNA molecular biology research, here are another
achievements that are related to RNA molecular research as well:

.Science: Revealing the association of circular RNA with brain function

Although we are clear that hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, an important problem
remains unresolved, that is, what role do they actually play? In a new study, Nikolaus Rajewsky and his team from the Max-
Delbrück Center for Molecular Medicine in Germany first associated a circRNA with brain function. The relevant research
results were published online in the journal Science.

Figure 1. Cdr1as is a brain-enriched circular RNA, expressed in hundreds of copies within neurons and essential for
maintaining normal brain function.

RNA is far more than just a communication between DNA and the proteins it encodes. Indeed, there are several different non-
coding RNA molecules. They can be long-chain non-coding RNAs (lncRNAs) or short regulatory RNAs (miRNAs) to
interfere with protein production (siRNA) or assist protein production (tRNA). In the past 20 years, scientists have discovered
about 20 kinds of RNAs that form complex network structures in the microscopic world of molecules, of which, circRNA is
the most mysterious one. As a class of unusual RNAs which heads are joined to their tails to form a covalently closed loop,
being considered as a rare foreign RNA species. In fact, current RNA sequencing analysis has revealed they are a large RNA
species that is highly expressed in brain tissue.

. Cell: A major breakthrough in discovering a new class of small RNA molecules that protect mammalian genomes

Our genome is a minefield, interspersed with potentially damaging DNA sequences, but hundreds of thousands of sentinels are
stationed on these DNAs. These sentinel, known as epigenetic markers, attach to these DNA double helices at these sites,
preventing them from playing the destructive role.
About half of the human genome consists of these destructive DNA sequences. They are ancient viruses and parasitic sequence
elements called transposon and retrotransposon that self-integrate into the human genome during long-term evolution.
Surprisingly, these sentinels were cleared and the genome was exposed during the two most critical processes of the life cycle.
Of course, these sentinels will return quickly, but will only return after a period of time when the epigenetic slate has been
wiped clean.

Figure 2. LTR-Retrotransposon Control by tRNA-Derived Small RNAs

Now, in a new study, researchers from the Cold Spring Harbor Laboratory (CSHL) in the United States found an emergency
replacement for these sentinels. In particular, these temporary protectors protect their genome during a very early period of
mammalian embryo development before they are implanted into the maternal uterine wall. The results of the study were
published in the Journal of Cell.

. Nature: First revealed a causal link between RNA splicing and aging

Aging is a key risk factor for a variety of devastating chronic diseases, but the biological factors that influence when and how
quickly the cells deteriorate over time are still largely unknown. Nowadays, a research team led by Harvard TH Chan School
of Public Health is the first to associate the function of a core component of cell splices (cleavage and re-ligation of RNA
molecules in a process called “RNA splicing” with the lifespan of nematodes. This finding will help to understand the
biological role of splicing in life and suggests that manipulating human-specific splicing factors may help promote healthy
aging. The relevant research results were published online in the journal of Nature.

As public health getting progresses, life expectancy has increased significantly over the past century in the world. Although
people generally live longer, they are still suffering from disease, especially in the last decade of life. Age-related diseases such
as cancer, heart disease, and neurodegenerative diseases are now an important global health burden, which is even getting
worse gradually.
The body and the cells must maintain a proper steady-state balance in order to maintain their youth, which means keeping the
biological information from the gene to the RNA to the protein flow in a smooth and appropriate balance at the cellular level.

. Cell: Clarifying the “mysterious journey” after RNA escapes from the nucleus

Cell will lock its DNA firmly in the nucleus, just like a password hidden in the vault. However, it may be a very challenging
task to strictly control the nuclear boundary. For cells, they must produce the necessary proteins, and DNA-based information
sometimes will escape away from the nucleus with some methods in the form of RNA molecules.

Recently, in a research report published in the international magazine Cell, researchers from Rockefeller University have
determined the structure of important components of the “restricted gate” in cells, which can allow many substances to pass,
including DNA transcription, RNA genetic information, etc.

Figure 3. mRNAs escape the nucleus with help from a nuclear pore subcomplex that sits directly over the transport channel in
the cytoplasm

. Nat Biotechnol: Scientists have successfully mapped out short-chain RNA molecules in single cells

Recently, a research report published in the international journal of Nature Biotechnology, researchers from the Caroline
College in Sweden successfully determined the absolute number of short-chain non-coding RNA sequences in a single
embryonic stem cell. While the information in a gene is used, such as when it encodes a protein, the DNA is first transcribed
into a messenger RNA as a model for protein production. Our body cells contain a large number of short-chain non-coding
RNA sequences that cannot produce proteins, and the researchers are not aware of the function of these RNA sequences. But
researchers are familiar with miRNAs, which interact with messenger RNA and regulate the function of genes and cells.
In this study, the researchers mapped short-stranded RNA sequences in individual cells. Previous studies of short-chain RNA
molecules were based on simultaneous analysis of many cells, which often made it difficult to study the specific functions of
short-chain RNA molecules. Professor Rickard Sandberg, one of the researchers said that, ‘We only have the general
understanding of short-chain RNA molecules, although we have mapped the general mechanisms of short-chain RNA
molecules, this still can not indicate the role these molecules play in different types of cells or diseases.’

References

1. Piwecka M, et al. Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain
function. Science, 2017, 357(6357).
2. Schorn A J,et al. LTR-Retrotransposon Control by tRNA-Derived Small RNAs. Cell, 2017, 170(1):61.
3. Heintz C, et al.Corrigendum: Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C.
elegans. Nature, 2017, 541(7635):102-106.
4. Fernandezmartinez J, et al. Structure and Function of the Nuclear Pore Complex Cytoplasmic mRNAExport
Platform. Cell, 2016, 167(5):1215-1228.e25.
5. Faridani O R, et al. Single-cell sequencing of the small-RNA transcriptome. Nature Biotechnology, 2016, 34(12):1264.

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