The role of lysosomes in helping RNA move around within a cell is explained in research published today in Cell.
A microscopic RNA molecule might need to travel as far as a meter to get from the nucleus of a nerve cell to its tip, where it's needed to make a protein. But exactly how RNA gets around has been "a long-standing question in the field"—and one with big implications for how cells work, reports Jennifer Lippincott-Schwartz from Howard Hughes Medical Institute's Janelia Reseach Campus.
RNA transportation is a key part of keeping a cell functioning properly. Often, it's dispatched to wherever the protein it codes for is needed, then translated into a protein on-site. So if RNA isn't distributed around a cell correctly, key proteins might not end up in the right places. That's a particularly big deal in large cells like neurons.
In a healthy neuron, RNA molecules cluster together with proteins to form "granules," packets of RNA that can be ferried around more easily than individual RNA strands. Then, a protein called Annexin A11 works like a power adaptor. It can latch onto both standard membrane-bound organelles, like lysosomes, and membraneless structures, like the RNA granules. Lysosomes easily zip around the cell. The adaptor protein allows RNA to take advantage of lysosomes' mobility and plug into a transportation network that would otherwise be inaccessible.
People with ALS often have mutations in the gene for Annexin A11, says Lippincott-Schwartz. Now, it's becoming clear how these mutations affect patients. When her team introduced mutations into the protein that mimic those seen in ALS patients, the RNA granules couldn't attach to the lysosomes. And if RNA can't get a ride to the places where it's needed to make proteins, neurons might have trouble either surviving or signaling properly to other cells.
Image: RNA granules (blue) move around cells by attaching to lysosomes (red). Image courtesy of Y. Liao et al./Cell 2019