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Ling-Ling Chen: Linking Long Noncoding RNA Processing and Function to RNA Biology

By Trends in Biochemical Sciences

Ling-Ling Chen studies long noncoding RNAs (lncRNAs), a giant and varied class of new RNA molecules. She has been a Principal Investigator at the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, China, since 2011. Her laboratory developed methods for genome-wide characterization of nonpolyadenylated RNAs, which led to the identification of broadly expressed intron-derived small nucleolar RNA-ended lncRNAs, circular intronic RNAs derived from intron lariats, and circular RNAs produced from back-spliced exons promoted by RNA pairing in flanking introns. These studies have uncovered unexpected types of lncRNAs with functional potential and roles for previously considered ‘junk’ introns in shaping complex mammalian transcriptomes.

Where are you from, and where has your scientific training and career taken you? What motivated you to become a scientist?

I received a BS in Biology from Lanzhou University, China, in 2000 and my MS in Pharmacology from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences in 2003. I like biology but I wasn’t really considering a research career until I started my PhD research with Gordon Carmichael at the UConn Health Center, USA, in 2004. Gordon is known for his studies on the polyomavirus life cycle and on RNA processing, editing, and function. His research is broad and his personality is generous. When I joined the lab Gordon allowed me to explore new directions for the lab. I had a feeling of ‘freedom’ in thinking and doing experiments in my own way. In Gordon's lab I first studied the function of a class of DNA elements in the human genome called Alu elements, which constitute more than 10% of all of the DNA. I found that inverted repeated Alu elements in the 3′-untranslated regions of mRNAs have the potential to form intramolecular double-stranded RNAs that act to retain mRNAs in particular nuclear substructures called paraspeckles. Then I found that the key to ‘Alu’ element-mediated gene regulation is a lncRNA called NEAT1 that itself serves as a scaffold to organize paraspeckles that are sites of storage for mRNAs that are not needed immediately in the cytoplasm. These findings not only represented a novel paradigm of gene regulation, but more importantly, during this process I acquired a ‘can-do attitude’, which has ever since greatly motivated me to be a productive scientist.

Is there a particular teacher or mentor who helped guide you on your path? What was special about their guidance, or how did they help you?

Yes. Gordon has been tremendously supportive in many ways. For example, he encouraged me to work on my own to pursue new directions even when I was a graduate student in his laboratory. He has always been encouraging and treated everything–both science and life–with a positive attitude. I think that both my training in Gordon's lab and what I have seen from Gordon were critically important for me to become a scientist.

What is your guiding philosophy in running your laboratory?

Before I was ready to choose to stay in academia, I finished an MBA degree in Management during my graduate study at UConn. At that time, I thought that the PhD–MBA dual degree would make me more competitive in the future job market. Although I ended up as a scientist, the MBA training indeed helped me a lot in running my lab in the beginning. I think that running a lab is very much like managing a small business where you need to generate ideas, identify your niche, raise money, set up the right culture, and recruit the right team to work with you. Plus, I also encourage everyone in the lab to learn and work with passion.

What do you like to do when you are not in the laboratory? Why?

I have often enjoyed city hiking (not shopping) when out of the lab. Hiking around a city, I could clear and refresh my mind. Until recently, I also liked reading books that are nonscientifically related such as romantic fiction. When enchanted with such fiction, I could completely but temporarily separate from my lab. However, this all changed when my daughter was born last year! Now I spend nearly all my off-lab time with my daughter:-).

What is your idea of perfect happiness?

To me there are two kinds of perfect happiness. One is with my family, especially my daughter. I never knew the joy of having a kid until I had her! Another kind of perfect happiness would be the same as many others who work as scientists and perhaps other fields. This is the rewarding feeling when I have confirmation of an answer to a challenging and long-standing unanswered question.

Why did you start working on your current research topic? (What first drew you to the question?)

In 2009, perhaps one of the most exciting discoveries in Molecular Biology was the widespread expression of the ‘mRNA-like’ lncRNAs that originate from intergenic regions. I worked on the lncRNA NEAT1 at that time and the long isoform of NEAT1 is nonpolyadenylated. So I asked myself the question: ‘Do all lncRNAs look similar to mRNAs?’ This idea motived me to search for additional novel types of lncRNAs in the nonpolyadenylated transcriptomes. At that time, I had just completed my PhD and had successfully applied for independent funding (a State of Connecticut Stem Cell Grant). I therefore began to develop methods to visualize and characterize nonpolyadenylated RNAs. This work, initiated in the USA but completed in China, has led to the discovery of several classes of RNA species in my lab located in Shanghai since 2011.

What was the most exciting question in your field right now?

Studies on lncRNAs are advancing at a rapid pace, but some characteristics of each lncRNA are still underappreciated. The recent advent of cutting-edge tools in Molecular Biology such as cryoelectron microscopy and gene-editing technologies has equipped RNA biologists with new ways to understand lncRNA molecules in greater detail. How different lncRNAs are processed, structured, and act as well as their distinctions and commonalities in gene regulation will be exciting to address in the future.


Ling-Ling Chen: Linking Long Noncoding RNA Processing and Function to RNA Biology (More Information)



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