On August 7, 2015, Science published “TDP-43 Repression of Nonconserved Cryptic Exons is Compromised in ALS-FTD” which describes the function of TDP-43, an important protein in amyotrophic lateral sclerosis (ALS, commonly referred to as Lou Gehrig’s disease). On the day of publication, the lead author used Reddit to announce the paper’s publication and answer some questions in the site’s popular Science Ask Me Anything (AMA) forum.
As librarians, what caught our eye was his ELI5 (“explain like I’m five”) analogy about cell functionality:
Cells in your body are constantly reading your DNA to make proteins.
DNA is located in the nucleus of a cell. You can think of a nucleus as a library except that instead of having books neatly lined up on shelves, the books in a nucleus have all of their pages ripped out and thrown around randomly.
To sort through this mess, the cell has great librarians that go around collecting all these pages, collating them and neatly binding them together as books. These librarians then ship these “books” out of the nucleus so that other workers in the cell can do their jobs. Think of these books as instruction manuals.
TDP-43 is a very special type of librarian. TDP-43’s job is to ensure that nucleus librarians don’t accidentally make a mistake and put a random nonsense page (usually filled with gibberish) into the books that they ship out. If one of these nonsense pages makes it into an “instruction manual”, the workers in the cell get really confused and mess things up. For terminology, we call these nonsense pages “cryptic exons”.