LncRNA: The Long and Short of “Junk RNA”

The Central Dogma and Junk DNA

lncRNA, long noncoding RNA

On September 19, 1957, Francis Crick delivered a lecture during a symposium at University College London, titled “Protein Synthesis”. The lecture was published a year later (1); in it, Crick quotes his colleague James Watson as saying, “The most significant thing about the nucleic acids is that we don’t know what they can do.” In contrast, Crick argued that proteins play a central, indispensable role as enzymes within the cell that catalyze a variety of chemical reactions. He believed that the main role of genetic material was to control the synthesis of proteins, although the mechanism of that process was not known.

Crick’s hypothesis came to be known as the central dogma of molecular biology, and it was immortalized in his hand-written notes that described the flow of information from DNA to RNA to proteins. This achievement was all the more remarkable, considering that messenger RNAs were completely unknown at that time, and very little was known about how the cellular translational machinery functioned within the cytoplasm to synthesize proteins. Although the later discovery of retroviruses appeared to challenge Crick’s central dogma, he explained quite succinctly that his original statement had simply been misunderstood, and that information could flow in both directions between DNA and RNA (2).

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Endpoint PCR in 15 Minutes with New Master Mix and Thermal Cycler Combination

Since its invention in 1983, the polymerase chain reaction (PCR) has become a fundamental technology in life science laboratories across the world. Much of the technological innovation is driven by quantitative PCR and digital PCR (1); however, endpoint PCR remains a workhorse technology for applications such as gene cloning, mutagenesis and detection of microbial pathogens. Variations on the basic endpoint PCR method—for example, the use of multiplexed, fluorescently labeled primers followed by capillary electrophoresis to analyze the amplified DNA fragments—are popular in forensic DNA analysis and cell line authentication.

The COVID-19 pandemic has created an urgent need for PCR-based diagnostic testing for SARS-CoV-2. Most of these diagnostic tests use real-time, reverse-transcription quantitative PCR (RT-qPCR). However, RT-qPCR can be challenging for routine use in developing countries and in laboratories with limited access to real-time PCR thermal cyclers. A recent study described an endpoint PCR method for SARS-CoV-2 detection to address these limitations (2).

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RNA-Protein Interactions: A New Frontier for Drug Discovery

Almost 90% of the human genome is transcribed into RNA, but only 3% is ultimately translated into a protein. Some non-translated RNA is thought to be useless, while some play a significant yet often mysterious role in cancer and other diseases. Despite its abundance and biological significance, RNA is rarely the target of therapeutics.

“We say it’s undruggable, but I would say that ‘not-yet-drugged’ is a better way to put it,” says Amanda Garner, Associate Professor of Medicinal Chemistry at the University of Michigan. “We know that RNA biology is important, but we don’t yet know how to target it.”

Amanda’s lab develops systems to study RNA biology. She employs a variety of approaches to analyze the functions of different RNAs and study their interactions with proteins. Her lab recently published a paper describing a novel method for studying RNA-protein interactions (RPI) in live cells. Amanda says that with the right tools, RPI could become a critical target for drug discovery.

“It’s amazing that current drugs ever work, because they’re all based on really old approaches,” Amanda says. “This isn’t going to be like developing a small molecule kinase inhibitor. It’s a whole new world.”

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Galloping to Greatness: Meet Kurt the First Cloned Przewalski’s Horse

Kurt the first cloned Przewalsk'si horse
Kurt the foal at the Texas veterinary facility of ViaGen Equine collaborator, Timber Creek Veterinary, August 28, 2020.
Photo provided courtesy of Scott Stine.

On August 6, 2020, the first successfully cloned Przewalski’s horse was born at the Texas-based veterinary facility, Timber Creek Veterinary, along with a new hope for restoring some much-needed genetic diversity to the species. The successful birth of this foal is the culmination of the collaborative efforts between Revive & Restore, San Diego Zoo Global (SDZG), and ViaGen Equine, and lays the groundwork as an important model for future conservation efforts.

The new Przewalski’s foal (pronounced “shuh-VAL-skees”) has been affectionately dubbed Kurt, in honor of noted animal conservationist, geneticist and pathologist, Dr. Kurt Benirschke. Dr. Benirschke played an instrumental role in founding the Frozen Zoo®, a genetic library comprised of cryopreserved cell lines of endangered species. Established in the 1970s, this collection was built on a foundation of prescient hope, banking on the future development of reproductive and cloning technologies that did not yet exist.

Now thanks to his foresight, that gamble is paying off and the fruits of that labor are literally being brought to life almost 50 years later through Kurt the foal, who is as adorable as he is important to the future of his kind.

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Identifying the Ancestor of a Domesticated Animal Using Whole-Genome Sequencing

What animal can be found around the globe that outnumbers humans three to one? Gallus gallus domesticus, the humble chicken. The human appetite for eggs and lean meat drive demand for this feathered bird, resulting in a poultry population of over 20 billion.

Controversy over the origin of the domestic chicken (when, where and which species) have lead some researchers to look for that information in the genomes of contemporary chicken breeds and wild jungle fowl, the candidates from which chickens were derived. By sequencing over 600 genomes from Asian domestic poultry as well as 160 genomes from all four wild jungle fowl species and the five red jungle fowl subspecies, Wang et al. wanted to understand and identify the relationships and relatedness among these species and derive where domesticated chickens first arose.

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XpressAmp™ Direct Amplification: Simplified and Accelerated Time to qPCR Results

As the SARS‐CoV‐2 pandemic continues to rage across the United States and around the globe, the demand for COVID‐19 testing is increasing. The vast majority of the COVID-19 assays use RT‐qPCR to detect the viral RNA in patient samples such as nasopharyngeal swabs, which are collected and stored in viral or universal transport media (VTM/UTM). The general workflow for these COVID‐19 assays can be broken down as follows:

  1. Collect and store patient samples
  2. Ship samples to testing laboratory
  3. Extract RNA from samples
  4. Amplify and analyze samples

While many companies who manufacture the products that are used in these steps have been able to adapt and significantly increase their production capacities, there are still gaps between the supply of these products and the global test demand. Both the sample collection and storage step and the RNA extraction/purification step have a tendency to bottleneck and experience supply constraints. One way to address these bottlenecks and expand production capacity for these in‐demand products is to evaluate the viability of skipping a step in the workflow, without hindering the ability to detect viral RNA from samples.

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Capillary Electrophoresis On Your Benchtop

Spectrum Compact CE System

Here’s the good news: The Spectrum Compact CE System is now available from Promega. 

Here’s the better news: Labs of all sizes now have the opportunity to perform Sanger sequencing and fragment analysis with a personal, benchtop instrument. 

There is no bad news. 

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Lessons in History, Hope and Living with Lynch Syndrome from the “Daughter of Family G”

Lynch Syndrome is the autosomal dominant hereditary predisposition to develop colorectal cancer and certain other cancers. This simple, one sentence definition seems woefully inadequate considering the human toll this condition has inflicted on the families that have it in their genetic pedigree.

They Called it a Curse

To one family, perhaps the family when it comes to this condition, Lynch Syndrome has meant heartache and hope; grief and joy; death and life. Their story is told by Ami McKay in her book Daughter of Family G, and it is at once both a memoir of a Lynch Syndrome previvor (someone with a Lynch Syndrome genomic mutation who has not yet developed cancer) and a poignant and honest account of the family that helped science put name to a curse.

“The doctors called it cancer. I say it’s a curse. I wish I knew what we did to deserve it.”

Anna Haab from Daughter of Family G (1)

The scientific community first met “Family G” as the meticulously created family tree, filled with the stunted branches that mark early deaths by cancer. The pedigree was first published in 1913 in Archives of Internal Medicine (2). In the article, Dr. Alderd Warthin wrote: “A marked susceptibility to carcinoma exists in the case of certain family generations and family groups.” In 1925, an expanded pedigree of circles and squares was published in Dr. Warthin’s follow up study in the Journal of Cancer Research (3).  But each circle and square in that pedigree denotes a person. Each line represents their dreams together for the future, and Ms. McKay wants us to know their names: Johannes and Anna, Kathrina, Elmer, Tillie, Sarah Anne (Sally); and—most importantly—Pauline. Because without Pauline there would be no story.

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What We Know About the COVID-19 and the SARS-CoV-2 Virus

David Goodsell image of SARS-2-CoV
Image by David Goodsell

In the nine months since the first cases of COVID-19 were noticed in Wuhan, China, the virus has spread around the globe and infected over 22 million people. As with all emerging infectious diseases, we often find ourselves with more questions than answers. However, through the tireless work of researchers, doctors and public health officials worldwide, we have learned a lot about the virus, how it spreads and how to contain it.

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Using the Power of Technology for Viral Outbreaks

Artist’s rendition of a virus particle.

When the world is experiencing a viral pandemic, scientists and health officials quickly want data-driven answers to understand the situation and better formulate a public health response. Technology provides tools that researchers can use to develop a rapid sequencing protocol. With such a protocol, the data generated can help answer questions about disease epidemiology and understand the interaction between host and virus. Even better: If the protocol is freely available and based on cheap, mobile sequencing systems.

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