RNA Silencing

RNA comes in many varieties. Silencing by small RNAs is linked to endosomal trafficking₁ is a paper detailing the function of what are known as small RNAs. The function alluded to in the paper is the regulation of messenger RNA (mRNA); the RNA transcript containing the genetic information subsequently translated to enable formation of amino acid polymers. Short interfering RNA (siRNA) and micro RNA (miRNA) are two RNA forms which interact with mRNA to effect what is known as silencing- the short circuiting of the translation process to prevent the synthesis of regulated proteins. From the abstract of the paper:

Small RNAs direct RNA-induced silencing complexes (RISCs) to regulate stability and translation of mRNAs1, 2. RISCs associated with target mRNAs often accumulate in discrete cytoplasmic foci known as GW-bodies3. However, RISC proteins can associate with membrane compartments such as the Golgi and endoplasmic reticulum4. Here, we show that GW-bodies are associated with late endosomes (multivesicular bodies, MVBs). Blocking the maturation of MVBs into lysosomes by loss of the tethering factor HPS4 (ref. 5) enhances short interfering RNA (siRNA)- and micro RNA (miRNA)-mediated silencing in Drosophila melanogaster and humans. It also triggers over-accumulation of GW-bodies. Blocking MVB formation by ESCRT (endosomal sorting complex required for transport)6 depletion results in impaired miRNA silencing and loss of GW-bodies. These results indicate that active RISCs are physically and functionally coupled to MVBs. We further show that MVBs promote the competence of RISCs in loading small RNAs. We suggest that the recycling of RISCs is promoted by MVBs, resulting in RISCs more effectively engaging with small RNA effectors and possibly target RNAs. It may provide a means to enhance the dynamics of RNA silencing in the cytoplasm.

Effective regulation of protein synthesis is a means of ensuring healthy ongoing cellular functions. Conversely impaired regulation can lead to serious diseases and even cancer.



Reference:

1. Silencing by small RNAs is linked to endosomal trafficking authored by Young Sik Lee, Sigal Pressman, Arlise P. Andress, Kevin Kim, Jamie L. White, Justin J. Cassidy, Xin Li, Kim Lubell, Do Hwan Lim, Ik Sang Cho, Kenji Nakahara, Jonathan B. Preall, Priya Bellare, Erik J. Sontheimer and Richard W. Carthew; Nature Cell Biology 11, 1150 - 1156 (2009).