Importance of an N-terminal structural switch in the distinction between small RNA-bound and free ARGONAUTE.

ARGONAUTE (AGO) proteins bind to small non-coding RNAs to form RNA-induced silencing complexes. In the RNA-bound state, AGO is stable while RNA-free AGO turns over rapidly. Molecular features unique to RNA-free AGO that allow its specific recognition and degradation remain unknown.

Ribosomal RNA 2'-O-methylation dynamics impact cell fate decisions.

Translational regulation impacts both pluripotency maintenance and cell differentiation. To what degree the ribosome exerts control over this process remains unanswered. Accumulating evidence has demonstrated heterogeneity in ribosome composition in various organisms.

Regulation of translation by site-specific ribosomal RNA methylation.

Ribosomes are complex ribozymes that interpret genetic information by translating messenger RNA (mRNA) into proteins. Natural variation in ribosome composition has been documented in several organisms and can arise from several different sources. A key question is whether specific control over ribosome heterogeneity represents a mechanism by which translation can be regulated.

Translational control through ribosome heterogeneity and functional specialization.

The conceptual origins of ribosome specialization can be traced back to the earliest days of molecular biology. Yet, this field has only recently begun to gather momentum, with numerous studies identifying distinct heterogeneous ribosome populations across multiple species and model systems. It is proposed that some of these compositionally distinct ribosomes may be functionally specialized and able to regulate the translation of specific mRNAs.

Profiling of 2'-O-Me in human rRNA reveals a subset of fractionally modified positions and provides evidence for ribosome heterogeneity.

Ribose methylation is one of the two most abundant modifications in human ribosomal RNA and is believed to be important for ribosome biogenesis, mRNA selectivity and translational fidelity. We have applied RiboMeth-seq to rRNA from HeLa cells for ribosome-wide, quantitative mapping of 2'-O-Me sites and obtained a comprehensive set of 106 sites, including two novel sites, and with plausible box C/D guide RNAs assigned to all but three sites. We find approximately two-thirds of the sites to be fully methylated and the remainder to be fractionally modified in support of ribosome heterogeneity at the level of RNA modifications.

MicroRNA and cancer.

With the advent of next generation sequencing techniques a previously unknown world of non-coding RNA molecules have been discovered. Non-coding RNA transcripts likely outnumber the group of protein coding sequences and hold promise of many new discoveries and mechanistic explanations for essential biological phenomena and pathologies. The best characterized non-coding RNA family consists in humans of about 1400 microRNAs for which abundant evidence have demonstrated fundamental importance in normal development, differentiation, growth control and in human diseases such as cancer.