Scientists discover another important role played by 'junk DNA'

Scientists have turned an old idea on its head. A new paper reports that stretches of so-called “junk DNA” can help injured nerve cells regrow by switching on a repair program.

Outside the brain and spinal cord, the peripheral nervous system (PNS) often bounces back after injury.

Inside the central nervous system (CNS), regrowth usually stalls, limited by a tough environment and a weaker internal drive to grow, as summarized in a recent review.

Junk DNA helps nerves

Leading the work is Professor Mike Fainzilber at the Weizmann Institute of Science. His team asked why some neurons recover briskly while others grind to a halt.

The answer points to short interspersed nuclear elements (SINEs) that are repeated throughout the genome.

These DNA repeats can be transcribed into non-coding RNA that does not make proteins, and Alu type SINEs alone account for roughly 10 percent of our genome.

“These high-copy-number sequences are like genomic parasites,” explained Indrek Koppel, Assistant Professor at the Department of Chemistry and Biotechnology at Tallinn University of Technology (Tal Tech).

“They sometimes like to replicate themselves, but as far as we know, they have been shown to do very little that is beneficial to the host.”

What the study found

Scientists discovered that after injury, certain sensory nerve cells start making special RNA molecules called GI-SINEs.

These RNAs are not used to build proteins directly, but they play an important role in helping nerves grow back. Interestingly, similar cells in the eye did not produce these RNAs under the same conditions.

When researchers increased GI-SINE levels, damaged nerves grew back farther. When they blocked the RNAs, growth slowed down.

One of the lead scientists explained that after an injury to the peripheral nervous system, neurons switch on these RNA molecules as part of their repair response.

Junk DNA repair switch

The team showed that GI-SINEs are linked to AP-1, a group of proteins that act like switches to turn on many repair genes.

Within that group, another protein, ATF3, stood out as especially important for pushing cells into a growth mode.

When AP-1 was blocked, GI-SINE levels dropped, and the repair program weakened. Removing ATF3 had the same effect.

This showed a clear chain of events: an injury activates AP-1 and ATF3, which then boost GI-SINEs, and those RNAs prepare the cell to regrow.

How GI-SINEs help inside the cell

The researchers found that GI-SINEs interact with a protein called nucleolin, which helps deliver important growth messages inside neurons.

Earlier work showed nucleolin plays a role in moving these messages to nerve fibers where proteins need to be made.

The team also saw GI-SINEs connecting with ribosomes, the cell’s protein factories. This suggests GI-SINEs help bring the right molecules together at the right spot to make proteins needed for regrowth.

Junk DNA missing in brain

One mystery in neuroscience is why nerves in the body can often regrow, while those in the brain and spinal cord usually cannot.

Some of the problem comes from the environment in the central nervous system, which creates chemical roadblocks. Another part is that brain and spinal neurons naturally have less ability to repair themselves.

This study adds a new layer: if CNS neurons do not produce GI-SINEs after injury, they may be missing an internal signal that helps organize the repair machinery.

That could be one reason for the difference in healing ability between body nerves and brain or spinal cord nerves.

Future treatments

Because dialing up GI-SINEs enhances growth in central neurons, one can imagine gene therapy or small molecules that nudge this RNA circuit in the brain or spinal cord.

The authors also showed that antisense oligonucleotides, designed to bind and block GI-SINEs, tamp down growth in sensory neurons, which hints at a way to tune aberrant sprouting if needed.

“Finding a function important for the nervous system in what had been considered a pile of genomic junk was new and unexpected,” Koppel expounded.

“Hopefully, this new perspective on the molecular mechanisms of nerve injury can be used in the development of innovative treatments for spinal cord or brain injuries, or even neurodegenerative diseases such as Alzheimer’s disease or ALS.”

Any future therapy will need to balance precision and safety. SINE elements are numerous, so targeting a specific, injury-induced subset, as done here, will be crucial.

The timing of intervention also matters. Protein synthesis and transport ebb and flow after injury in a tight sequence, so therapies that align with that rhythm should work better than constant, untimed boosts.

Future research on junk DNA

Independent labs will need to confirm that similar SINE-derived RNAs exist and act in human neurons, not only in the models used here.

It will also be important to map which mRNAs benefit most from the GI-SINE, nucleolin, and ribosome partnership and which tissues tolerate that shift.

Another question is how long the pro-growth window should remain open. Cells will need to close it again to stabilize circuits, so an on switch without an off switch could cause trouble.

Finally, the AP-1 and ATF3 linkage raises a practical point. Some approved drugs modulate these pathways indirectly, which could speed translation of the basic biology into early clinical tests.

The study is published in Cell.

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