Research Roundup: What Are Microproteins and What Do They Do and More


Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones.

The Role of the Mysterious Microproteins

Genes code for proteins. Prior to the Human Genome Project, the Central Dogma was that one gene coded for one protein. And since there were about 100,000 known proteins, scientists believed there were 100,000 human genes. But there weren’t, there were about 20,000 genes and proteins are created by reading those genes in various ways—from beginning to end, backwards, starting in the middle, etc. Now researchers are increasingly finding what are called microproteins, which have fewer than 100 amino acids, and are discovering that they microproteins may have more fundamental effects on cellular processes than previously thought.

Researchers with the Salk Institute published research in the journal Nature Communications on the role of 54-amino acid microprotein PIGBOS and how it mitigates cell stress.

“The study is exciting because cell stress is important in a number of different diseases, including cancer and neurodegeneration,” said Alan Saghatelian, co-corresponding author of the research. “By understanding the mechanisms behind these diseases, we think we’ll have a better shot at treating them.”

The researchers used a technique called split GFP to tag the microprotein, which was too small for the more traditional green fluorescent protein (GFP) tags. While mapping PIGBOs’ location, they found that it rests on the outer membrane of the mitochondria, which puts it in position to make contact with proteins on other organelles. They found that it interacted with another protein, CLCC1, which is part of the endoplasmic reticulum (ER) and communicates with CLCC1 to regulate stress in the ER.

“PIGBOS represents one of a limited set of microproteins that anyone has gone through the effort to characterize,” said co-corresponding author Uri Manor, director of the Waitt Advanced Biophotonics Core Facility at Salk. “And lo and behold it actually has a very important role.”

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Natural Monkey Mutation Provides Model for Rare Human Blindness

Researchers identified a mutated gene in three rhesus monkeys that is associated with Bardet-Biedl Syndrome (BBS), a rare genetic disease that causes childhood-onset blindness. The science team indicates it is the first naturally occurring case of a nonhuman primate model of the syndrome and could lead to potential treatments. The BBS genes encode proteins for the function of cilia. Models of BBS have been developed from rodents, fish and roundworms, but they are not as closely related to human eyes as primate models.

Newly Found Antibody Could Be Basis of Universal Flu Vaccine

Researchers at The Scripps Research Institute, the Washington University School of Medicine in St. Louis and Icahn School of Medicine at Mount Sinai in New York identified an antibody that protects mice against a wide range of flu viruses. The antibody binds to the protein neuraminidase, which flu viruses require to replicate in the body. It is located on the surface of the virus. Tamiflu, the best-known drug to fight flu, inactivates neuraminidase. But there are numerous types of neuraminidases. This antibody could be the foundation of a universal flu vaccine.

Neural Activity and Longevity

A protein called REST has previously been shown to protect aging brains from dementia and other neurodegenerative diseases. Now researchers have identified REST as essential in a molecular cascade related to aging. The study found that excessive brain activity in humans, mice and worms is associated with shorter life spans. Suppressing that overactivity extends life. REST is part of a signaling cascade that includes the insulin and insulin-like growth factor (IGF) pathway. It’s not clear on whether or how a person’s thought, personality or behavior, within this context, affects longevity.

A Smell Test for Alzheimer’s Disease?

People who performed well on a test measuring cognitive ability and another to identify odors were linked to very low risk of Alzheimer’s disease. The tests have previously been shown to help predict the risk of developing dementia, but this study suggests the tests could help rule out people unlikely to develop Alzheimer’s. The researchers analyzed data from 749 adults with mild cognitive impairment without dementia who had completed a cognitive screening test and a 40-item smell identification test. They were then followed for four years to find whether they were later diagnosed with Alzheimer’s or other dementias. During that period, 109 people developed dementia with most diagnosed with Alzheimer’s. But the research found that 96.5% of the participants who performed well on both tests did not develop dementia during the study period.

Anti-inflammatory Drugs Can Decrease Major Depressive Symptoms

A pooled analysis found that anti-inflammatory agents like aspirin/paracetamol, statins, and antibiotics can curb symptoms of major depression. The effects are even stronger when the anti-inflammatories are given in combination with standard antidepressants. Previous studies of anti-inflammatories to treat depression were inconclusive, but this pooled analysis of 26 of 30 relevant randomized controlled trials involving 1,610 people suggested the anti-inflammatories were better than placebo and improved the effects of standard antidepressants.

Medicinal Cannabinoids Don’t Improve Mental Health

Researchers analyzed the impact of medicinal cannabinoids on six mental health disorders from 83 studies including 3,000 people. They found that the use of cannabinoids can’t be justified based on the current evidence. The conclusion was based on lack of proof of effectiveness and the known risks of cannabinoids. The medicinal cannabinoids include medical cannabis and pharmaceutical cannabinoids and their synthetic derivatives, THC and CBD. The six mental health disorders in adults were: depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder (PTSD), and psychosis.

How a Key Gene Linked to Familiar Alzheimer’s Functions

A gene that is mutated in familial Alzheimer’s disease is called presenilin. Although linked to the disease, it wasn’t completely understood how this functioned. A research group found that the malfunction in this gene causes the abnormal accumulation of beta-amyloid in the brain. Presenilin is not only essential for regulating neuronal growth, but it does so through the EphaA3 receptor, a protein linked to several cancers.

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