Telomeres are special DNA-protein structures that are located at the ends of linear eukaryotic chromosomes. The telomere length determines the proliferation potential of cells. Telomerase is a key component of the telomere length maintenance system. While telomerase is inactive in the majority of somatic cells, its activity determines the clonogenic potential of stem cells as a resource for tissue and organism regeneration. Reactivation of telomerase occurs during the process of immortalization in the majority of cancer cells. Telomerase is a ribonucleoprotein that contains telomerase reverse transcriptase and telomerase RNA components. The RNA processing mechanism of telomerase involves exosome trimming or degradation of the primary precursor. Recent data provide evidence that the competition between the processing and decay of telomerase RNA may regulate the amount of RNA at the physiological level. We show that termination of human telomerase RNA transcription is dependent on its promoter, which engages with the multisubunit complex Integrator to interact with RNA polymerase II and terminate transcription of the human telomerase RNA gene followed by further processing.

Several studies have described functional peptides encoded in RNA that are considered to be noncoding. Telomerase RNA together with telomerase reverse transcriptase and regulatory proteins make up the telomerase complex, the major component of the telomere length-maintaining machinery. In contrast to protein subunits, telomerase RNA is expressed constitutively in most somatic cells where telomerase reverse transcriptase is absent. We show here that the transcript of human telomerase RNA codes a 121 amino acid protein (hTERP). The existence of hTERP was shown by immunoblotting, immunofluorescence microscopy and mass spectroscopy. Gain-of-function and loss-of-function experiments showed that hTERP protects cells from drug-induced apoptosis and participates in the processing of autophagosome. We suggest that hTERP regulates crosstalk between autophagy and apoptosis and is involved in cellular adaptation under stress conditions.

Telomerase is an enzyme that maintains the length of the telomere. The telomere length specifies the number of divisions a cell can undergo before it finally dies (i.e. the proliferative potential of cells). For example, telomerase is activated in embryonic cell lines and the telomere length is maintained at a constant level; therefore, these cells have an unlimited fission potential. Stem cells are characterized by a lower telomerase activity, which enables only partial compensation for the shortening of telomeres. Somatic cells are usually characterized by the absence of telomerase activity. Telomere shortening leads to the attainment of the Hayflick limit, the transition of cells to a state of senescence. The cells subsequently enter a state of crisis, accompanied by massive cell death. The surviving cells become cancer cells, which are capable both of dividing indefinitely and maintaining telomere length (usually with the aid of telomerase). Telomerase is a reverse transcriptase. It consists of two major components: telomerase RNA (TER) and reverse transcriptase (TERT). TER is a non-coding RNA, and it contains the region which serves as a template for telomere synthesis. An increasing number of articles focussing on the alternative functions of telomerase components have recently started appearing. The present review summarizes data on the structure, biogenesis, and functions of telomerase.

First triplets of mRNA coding region affect the yield of translation. We have applied the flowseq method to analyze >30 000 variants of the codons 2–11 of the fluorescent protein reporter to identify factors affecting the protein synthesis. While the negative influence of mRNA secondary structure on translation has been confirmed, a positive role of rare codons at the beginning of a coding sequence for gene expression has not been observed. The identity of triplets proximal to the start codon contributes more to the protein yield then more distant ones. Additional in-frame start codons enhance translation, while Shine–Dalgarno-like motifs downstream the initiation codon are inhibitory. The metabolic cost of amino acids affects the yield of protein in the poor medium. The most efficient translation was observed for variants with features resembling those of native Escherichia coli genes.

Mammalian mitochondrial ribosomes contain a set of modified nucleotides, which is distinct from that of the cytosolic ribosomes. Nucleotide m⁴C840 of the murine mitochondrial 12S rRNA is equivalent to the dimethylated m⁴Cm1402 residue of Escherichia coli 16S rRNA. Here we demonstrate that mouse METTL15 protein is responsible for the formation of m⁴C residue of the 12S rRNA. Inactivation of Mettl15 gene in murine cell line perturbs the composition of mitochondrial protein biosynthesis machinery. Identification of METTL15 interaction partners revealed that the likely substrate for this RNA methyltransferase is an assembly intermediate of the mitochondrial small ribosomal subunit containing an assembly factor RBFA.

Telomerase is a ribonucleoprotein complex that maintains the lengths of telomeres. Most studies of telomerase function have focused on the involvement of telomerase activation in the immortalization of cancer cells and cellular rejuvenation. However, some studies demonstrated that the results do not meet expectations for telomerase action in telomere maintenance. Recent results give reason to think that major telomerase components—the reverse transcriptase protein subunit and telomerase RNA—may participate in many cellular processes, including the regulation of apoptosis and autophagy, cell survival, pro-proliferative effects, regulation of gene expression, and protection against oxidative stress. However, the difficulties faced by scientist when researching telomerase component functions often reduce confidence in the minor effects observed in experiments. In this review, we focus on the analysis of the functions of telomerase components (paying more attention to the telomerase RNA component), both as a complex and as independent components, providing effects that are not associated with telomerase activity and telomere length maintenance. Despite the fact that the data on alternative roles of telomerase components look illusory, it would be wrong to completely reject the possibility of their involvement in other biological processes excluded from research/discussion. Investigations to improve the understanding of every aspect of the functioning of telomerase components will provide the basis for a more precise development of approaches to regulate cellular homeostasis, which is important for carcinogenesis and aging.